Chapter 6 : Genetic Addiction: a Principle of Gene Symbiosis in a Genome

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Genetic Addiction: a Principle of Gene Symbiosis in a Genome, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817732/9781555812652_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555817732/9781555812652_Chap06-2.gif


Observations suggest that the genome is a community of genes that essentially act selfishly and potentially do not have the overall order of the genome as their primary interest. Postsegregational host killing maintains the existence of a genetic element by death. This chapter extracts general rules whereby death is used to govern genomes. It reviews the development of the concept of genetic addiction, and introduces several types of addiction systems. The chapter examines where the addiction modules are located in genomes and how they get there, and discusses their mechanisms of action and their gene expression regulation, which include contributions from structural studies. It sketches various kinds of interactions that take place between addiction systems within a genome and then addresses the central paradox: why a genetic element that is potentially toxic to the genome is ever maintained. The chapter then reviews the evidence that suggests that some forms of genetic addiction have affected genome evolution. Further, the chapter extrapolates these arguments, which are based on bacterial systems, to genome biology in general. Finally, it summarizes the various ways addiction systems can be used in experimental biology, biotechnology, and medicine. The concept of genetic addiction may prove to be one of the most fruitful contributions from plasmid biology to the understanding of life.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

The principle of genetic addiction. (A) Once established in a cell, the addiction module is difficult to eliminate because its loss, or some sort of threat to its persistence, leads to cell death. Intact copies of the module survive in the other cells of the clone, (B) Advantage of postsegregational killing in competitive exclusion between genetic elements in a genome. A specific case of postsegregational cell killing shows the fight of the module against an incoming competing genetic element.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Stabilization of maintenance of a plasmid by carriage of restriction-modification gene complex and its suppression by M.SsoII. The bacterial cells with a plasmid (RII R*M* [filled circle]; RII R'M* [open circle]) or with two plasmids (RII R*M* and Sso11 R*M* [filled triangle]) were grown in liquid medium after removal of the selection for the RII plasmid (but with selection for the Sso11 plasmid). The culture was continued with appropriate dilutions. Then cells were spread on agar to determine the fraction of viable cells carrying the R11 plasmid. The number of viable cells was used to calculate generation numbers on the horizontal axis. Modified from ( ) with permission of Oxford University Press.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

A generalized mechanism of genetic addiction. Classification of genetic addiction systems by action of the antitoxin is also included. See text ("Types of Genetic Addiction") for explanation.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Three types of genetic addiction. The classification of addiction systems on the basis of the way the antitoxin blocks the activity of the toxin is shown. See text ("Types of Addiction") for explanation.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Organization and regulation of addiction modules. A pointed box indicates a gene together with its direction. A thick arrow indicates transcription. The black and gray circle, triangle, and squares indicate gene products. The plus sign indicates a positive effect of the protein on gene expression, while the minus sign indicates a negative effect. See Table 2 and text for references.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Contribution of addiction genes to large genome polymorphism, psk: a postsegregational killing gene complex or an addiction module. In A, the boxes indicate open reading frames constituting an operon-like gene cluster. An arrow indicates transcription. In B. a thick arrow indicates a duplicated sequence that is in the order of 100 bp in length. In D, the bent arrows indicate a segment in the order of 10 kbp in length that appears inverted when two genomes are compared. In E, the double lines marked as psk indicate two regions highly homologous with each other and carrying a postsegregational killing module homologue.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

Postsegregational killing by a restriction-modification module. (A) Restriction enzyme (toxin) and modification methyltransferase (antitoxin). The antitoxin protects the targets of the toxin by methylation. (B) Postsegregational killing by simple dilution. After loss of the restriction-modification gene complex, the toxin (restriction enzyme) and antitoxin (modification enzyme) will become increasingly diluted after cell division. Finally, too few modification enzyme molecules remain to defend all (or sufficiently many) of the recognition sites present on the newly replicated chromosomes. Any one of the remaining molecules of the restriction enzyme can attack these exposed sites. The chromosome breakage then leads to extensive chromosome degradation, and the cell dies unless the breakage is somehow repaired. The chromosome breakage may stimulate recombination and generate a variety of rearranged genomes, some of which might survive.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8
Figure 8

A model for the action of the RelE/RelB system. Genetic organization and regulatory components of the toxinantitoxin operon (left), the site of mRNA cleavage hy RelE (middle), and ribosome rescue by tmRNA (right). Modified from reference with permission of Blackwell Publishing.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 9
Figure 9

Interaction between two addiction systems that forces host killing. (A) Invasion and establishment of an addiction module in a new host cell. The regulatory system of the module allows the antitoxin to be expressed first to prevent host cell killing by the toxin. This addiction module thus successfully establishes itself in this new host cell. (B) Superinfection exclusion upon invasion of an addiction module into a cell that harbors another addiction module with similar specificity in its regulatory system. The regulatory system of the resident complex forces the incoming system to express its toxin first. The cell is killed and the establishment of the incoming addiction module is aborted. The resident addiction gene complex survives in the neighboring clonal cells. This represents another example of defense by cell death (see Fig. 1B ).

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 10
Figure 10

Interaction between two addiction systems that prevents host killing. (A) Postsegregational killing programmed by one addiction system. This addiction molecule can force its maintenance on the host. (B) Inhibition of this postsegregational killing by another addiction system. Antitoxin 2 may inhibit action of toxin 1 after loss of addiction module 1 by interacting with it at the protein level (type A, classical proteic system), by protecting its target (type B. restriction-modification system), or by blocking its gene expression (type C, antisense-RNA-regulated system). Addiction module 1 cannot force its maintenance on the host.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 11
Figure 11

The chromosome as a vehicle for mutual addiction among genes. (A) Chromosome breakage by a methylatcd-DNA-specific endonuclease in defense against an invading addiction module. An addiction module (more specifically, a restriction-modification module) enters a cell and starts modifying its target (methylating chromosomal recognition sites). A solitary toxin (a merhylated-DNA-specific endonuclease) senses these changes and triggers cell suicide (by chromosomal cleavage and degradation). The uninfected genome survives in the neighboring clonal cells. (B) Chromosome breakage by an endonuclease in defense against alteration of a gene. Some alteration, such as DNA damage, takes place on gene a in a chromosome. An endonuclease recognizes this alteration and makes a DNA break there. This suicide of gene can lead to loss of all the remaining genes in the chromosome and cell death. The unaltered genome survives in the neighboring clonal cells. Each gene on the chromosome can thus force its maintenance on the genome by postdisturbance cell killing through chromosome breakage. (C) The hypothetical case when each gene is on an independent replication unit. Suicide of one altered gene by DNA breakage cannot lead to loss of all the remaining genes and cell death. A gene thus cannot force its maintenance on the genome. Me, methyl group on the chromosome; a, b, c, gene , gene , gene

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 12
Figure 12

A genetic addiction hypothesis for the origin of the eukaryotes. Protomitochondriai bacteria entered anaerobic cells to form the ancestral eukaryote cells. The protomitochondria killed the host when there was disturbance to their perpetuation. This host killing resulted in their apparently stable symbiosis with the eukaryote cell. The system of mitochondria-mediated cell death has been inherited in multicellular eukaryotes that include mammals.

Citation: Kobayashi I. 2004. Genetic Addiction: a Principle of Gene Symbiosis in a Genome, p 105-144. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adams, G. M. and R. M. Blumenthal. 1995. Gene pvullW: a possible modulator of Pvull endonuclease subunit association. Gene 157: 193 199.
2. Adler, E.,, I. Barak,, and P. Stragier. 2001. Bacillus subtilis locus encoding a killer protein and its antidote. J. Bacteriol. 183: 3574 3581.
3. Afif, H.,, N. Allali,, M. Couturier,, and L. Van Melderen. 2001. The ratio between CcdA and CcdB modulates the transcriptional repression of the ccd poison-antidote system. Mol. Microbiol. 41: 73 82.
4. Aizenman, E.,, H. Engelberg-Kulka,, and G. Glascr. 1996. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphatc: a model for programmed bacterial cell death. Proc. Natl. Acad. Sci. USA 93: 6059 6063.
5. Allali, N.,, H. Afif,, M. Couturier,, and L. Van Melderen. 2002. The highly conserved TldD and TldE proteins of Escherichia coli are involved in microtia Bl 7 processing and in CcdA degradation. J. Bacteriol. 184: 3224 3231.
6. Aim, R. A.,, L. S. Ling,, D. T. Moir,, B. L. King,, E. D. Brown,, P. C Doig,, D. R. Smith,, B. Noonan,, B. C Guild,, B. L. dcjonge,, G. Carmcl,, P. J . Tummino,, A. Caruso,, M. Uria- Nickelsen,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang, D, E. Taylor, G. F, Vovis, and T. J. Trust. 1999. Gcnomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397: 176 180.
7. Alvarez, M. A.,, K. F. Chatcr,, and M. R. Rodicio. 1993. Complex transcription of an operon encoding the Sail restriction-modification system of Streptomyces albus G. Mol. Microbiol. 8: 243 252.
8. Ameisen, J., 1998. The evolutionary origin and role of programmed cell death in single-celled organisms: a new view at executioners, mitochondria, host-pathogen interactions, and the role of death in the process of natural selection, p. 3 56. In R. A. Lockshin,, Z. Zakeri,, and J. L. Tilly (ed.), When Cells Die: A Comprehensive Evaluation of Apoptosis and Programmed Cell Death. Wiley-Liss, New York, N.Y..
9. Ameisen, J . C. 2002. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death and Differentiation 9: 367 393.
10. Anton, B. P.,, D. F. Heiter,, J. S. Benner,, E. J. Hess,, L. Greenough,, L. S. Moran,, B. E. Slatko,, and J. E. Brooks. 1997. Cloning and characterization of the Bg/II restriction-modification system reveals a possible evolutionary footprint. Gene 187: 19 27.
11. Aras, R. A.,, T. Takata,, T. Ando,, A. van der Endc,, and M. J . Blascr. 2001. Regulation of the Hpyll restriction-modification system of Helicobacter pylori by gene deletion and horizontal reconstitution. Mol. Microbiol 42: 369 382.
12. Arnold, D. A.,, N. Handa,, I. Kobayashi,, and S. C. Kowalczykowski. 2000. A novel, 1l-nucleotide variant of x, X*: one of a class of sequences defining the E. coli recombination hotspot, x. J. Mol. Biol. 300: 469 479.
13. Bailone, A.,, A. Brandenburger,, A. Levine,, M. Pierre,, M. Dutrcix,, and R. Devoret. 1984. Indirect SOS induction is promoted by UV-damaged miniF and requires the miniF lynA locus. J. Mol Biol 179: 367 390.
14. Bart, A.,, J. Dankert, and A, van der Ende. 1999. Operator sequences for the regulatory proteins of restriction modification systems. Mol. Microbiol. 31: 1277 1278.
15. Baum, J.A.. 1994. Tn5401, a new class II transposable element from Bacillus tburingiettsis. J. Bacteriol. 176: 2835 2845.
17. Beletskaya, I. V.,, M. V. Zakharova,, M. G. Shlyapnikov,, L. M. Semenova,, and A. S. Sotonin. 2000. DNA methylation at the CfrBl site is involved in expression control in the CfrBI restriction-modification system. Nucleic Acids Res. 28: 3817 3822.
18. Bennetzen, J. L. 2000. Transposable clement contributions to plant gene and genome evolution. Plant Mol. Biol. 42: 251 269.
19. Bergstrom, C. T.,, M. Lipsitch,, and B. R. Levin. 2000. Natural selection, infectious transfer and the existence conditions for bacterial plasmids. Genetics 155: 1505 1519.
20. Bernard, P.,, and M. Couturier. 1992. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase 11 complexes. J. Mol. Biol. 226: 735 745.
21. Bernard, P.,, P. Gabant,, E. M. Bahassi,, and M. Couturier. 1994. Positive-selection vectors using the F plasmid ccdB killer gene. Gene 148: 71 74.
22. Bernard, P.,, K. E. Kezdy,, L. Van Melderen,, J . Steyaert,, L. Wyns,, M. L. Pato,, P. N. Higgins,, and M. Couturier. 1993. The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase. J. Mol Biol 234: 534 541.
23. Bishop, R. E. B. K. Leskiw, R. S. Hodges, C. M. Kay, and J. H. Weiner. 1998. The entericidin locus of Escherichia coli and its implications for programmed bacterial cell death. J. Mol. Biol. 280: 583 596.
24. Borek, E.,, and A. Ryan. 1958. The transfer of irradiation-elicited induction in a lysogenic organism. Proc. Natl. Acad. Sci. USA 44: 374 377.
25.Bravo. A., G. de Torrontegui, and R. Diaz. 1987. Identification of components of a new stability system of plasmid Rl. ParD, that is close to the origin of replication of this plasmid. Mol. Gen. Genet. 210: 101110.
26. Bravo, A.,, S. Ortega,, G. de Torrontcgui,, and R. Diaz. 1988. Killing of Escherichia coli cells modulated by components of the stability system ParD of plasmid Rl. Mol. Gen. Genet. 215: 146 151.
26a.. Brown,, J. M.,, and K. J. Shaw, 2003. A novel family of Escherichia coli toxin-antitoxin gene pairs. Bacteriol. 185: 6600 6608.
27. Bujnicki, J. M. 2001. Understanding the evolution of restriction- modification systems: clues from sequence and structure comparisons. Acta. Biochim. Pol. 48: 935 967.
28. Burrus, V., C Bontemps, B. Decaris, and G. Guedon. 2001. Characterization of a novel type II restriction-modification system, Sth368I, encoded by the integrative element ICEStl of Streptococcus thermophilus CNRZ368. Appl. Environ. Microbiol. 67: 1522 1528.
29. Butler, D.,, and G. F. Fitzgerald. 2001. Transcriptional analysis and regulation of expression of the ScrFI restriction-modification system of Lactococcus lactis subsp. cremoris UC503 J. Bacteriol 183: 4668 4673.
30. Calvin Koons, M. D.,, and R. M. Blumenthal. 1995. Characterization of pPvul, the autonomous plasmid from Proteus vulgaris that carries the genes of the PvuII restriction- modification system. Gene 157: 73 79.
31. Camacho, A. G.,, R. Misselwitz,, J . Behlke,, S. Ayora,, K. Welfle,, A. Meinhart,, B. Lara,, W. Saenger,, H. Welfle,, and J. C. Alonso. 2002. In vitro and in vivo stability of the epsilon2zeta2 protein complex of the broad host-range Streptococcus pyogenes pSM 19035 addiction system. Biol Chem. 383: 1701 1713.
32. Ceglowski, P.,, A. Boitsov,, S. Chai,, and J. C. Alonso. 1993. Analysis of the stabilization system of pSM19035-derived plasmid pBT233 in Bacillus subtilis. Gene 136: 1 12.
33. Cesnaviciene, E.f G. Mitkaite, K. Stankevicius, A. Janulaitis, and A. Lubys. 2003. Esp 13961 restriction-modification system: structural organization and mode of regulation. Nucleic Acids Res. 31: 743 749.
34. Chao, L.,, and B. R. Levin. 1981. Structured habitats and the evolution of anticompetitor toxins in bacteria. Proc. Natl Acad. Sci. USA 78: 6324 6328.
35. Cheng, X.,, K. Balendiran, I Schildkraut, and J. E. Anderson. 1994. Structure of PvuII endonuclease with cognate DNA. EMBO J. 13: 3927 3935.
36. Cheng, X.,, and R. J. Roberts. 2001. AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res. 29: 3784 3795.
37. Chinen, A.,, Y. Naito,, N. Handa, and I Kobayashi. 2000. Evolution of sequence recognition by restriction-modification enzymes: selective pressure for specificity decrease. Mol. Biol. Evol. 17: 1610 1619.
38. Chinen, A.,, I. Uchiyama,, and I. Kobayashi. 2000. Comparison between Pyrococcus borikoshii and Pyrococcus abyssi genome sequences reveals linkage of restriction-modification genes with large genome polymorphisms. Gene 259: 109 121.
39. Choi, Y. J.,, T. T. Wang,, and B. H. Lec. 2002. Positive selection vectors. Crit. Rev. Biotechnol. 22: 225 244.
40.Christensen. S. K., and K, Gerdes. 2003. RelE toxins from Bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol Microbiol. 48: 13891400.
41. Christensen, S. K.,, M. Mikkelscn,, K. Pedersen,, and K. Gerdes. 2001. RelE, a global inhibitor of translation, is activated during nutritional stress. Proc. Natl. Acad. Sci. USA 98: 14328 14333.
41a. Christensen,, S. K.,, K. Pedersen,, F. G. Hansen,, and K. Gerdes. 2003. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave RNAs and are counteracted by tmRNA. J. Mol Biol. 332: 809 819.
42. Claus, H.,, A. Friedrich,, M. Frosch,, and U. Vogel. 2000. Differential distribution of novel restriction-modification systems in clonal lineages of Neisseria meningitidis. J. Bacteriol 182: 1296 1303.
43. Cooper, T. F.,, and J . A. Heinemann. 2000. Postsegregational killing does not increase plasmid stability but acts to mediate the exclusion of competing plasmids. Proc. Natl Acad. Sci. USA 97: 12643 12648.
44. Cooper, T. F.,, D. E. Rozen,, and R. E. Lenski. 2003. Parallel changes in gene expression after 20,000 generations of evolution in Escherichia coli. Proc. Natl. Acad. Sci. USA 100: 1072 1077.
45. Couturier, M.,, E. M. Bahassi,, and L. Van Melderen. 1998. Bacterial death by DNA gyrase poisoning. Trends Microbiol. 6: 269 275.
46. Critchlow, S. E,, M. H. O'Dea, A.J. Howells, M. Couturier, M. Gellert, and A. Maxwell. 1997. The interaction of the F plasmid killer protein, CcdB, with DNA gyrase: induction of DNA cleavage and blocking of transcription. J. Mol. Biol. 273: 826 839.
47. Cromie, G. A.,, and D. R. Leach. 2001. Recombinational repair of chromosomal DNA double-strand breaks generated by a restriction endonuclease. Mol Microbiol. 41: 873 883.
48. Dao-Thi, M. H.,, D. Charlier,, R. Loris,, D. Macs,, J. Messens,, L. Wyns,, and J . Backmann. 2002. Intricate interactions within the ccd plasmid addiction system. J. Biol. Chem. 277: 3733 3742.
49. De Bolle, X.,, C. D. Bayliss,, D. Field,, T. van de Ven,, N. J. Saunders,, D. W. Hood,, and E. R. Moxon. 2000. The length of a tctranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol Microbiol. 35: 211 222.
50. de Feyter, R.,, C. Wallace,, and D. Lane. 1989. Autoregulation of the ccd operon in the F plasmid. Mol. Gen. Genet. 218: 481 486.
51. de la Cueva-Mendez, G.,, A. D. Mills,, L. Clay-Farrace,, R. Diaz-Orejas,, and R. A. Laskey. 2003. Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis. EMBO J. 22: 246 251.
52. de la Hoz, A. B.,, S. Ayora,, I. Sitkiewiez,, S. Fernandez,. R. Pankiewiez,, J. C. Alonso,, and P. Ceglowski. 2000. Plasmid copy-number control and better-than-random segregation genes of pSM 19035 share a common regulator. Proc. Natl. Acad. Sci. USA 97: 728 733.
53. de Vries, N.,, D. Duinsbergen,, E. J. Kuipers,, R. G. Pot,, P. Wiesenckker,, C. W. Penn,, A. H. van Vliet,, C. M. Vandenbroucke- Grauls,, and J. G. Kusters. 2002. Transcriptional phase variation of a type HI restriction-modification system in Helicobacter pylori. J. Bacteriol 184: 6615 6623.
54. Doronina, V. A.,, and N. E. Murray. 2001. The proteolytic control of restriction activity in Escherichia coli K-12. Mol. Microbiol. 39: 416 428.
55. Dybvig, K.,, R. Sitaraman,, and C. T. French. 1998. A family of phase-variable restriction enzymes with differing specifici ties generated by high-frequency gene rearrangements. Proc. Natl Acad. Sci. USA 95: 13923 13928.
56.Easter, C L., P. A. Sobecky, and D. R. Helinski. 1997. Contribution of different segments of the par region to stable maintenance of the broad-host-range plasmid RK2. J. Bacteriol. 179: 64726479.
57. Eddy, S. R.,, and L. Gold. 1992. Artificial mobile DNA element constructed from the EcoR1 endonuclease gene. Proc. Natl Acad. Sci. USA 89: 1544 1547.
58. el Karoui, M.,, D. Ehrlich,, and A. Gruss. 1998. Identification of the lactococcal cxonuclease/recombinase and its modulation by the putative chi sequence. Proc. Natl Acad. Sci. USA 95: 626 631.
59. Engelberg-Kulka, H.,, and G. Glaser. 1999. Addiction modules and programmed cell death and antideath in bacterial cultures. Annu. Rev. Microbiol. 53: 43 70.
60. Engelberg-Kulka, H.,, M. Reches,, S. Narasimhan,, R. Schoulaker-Schwarz,, Y. Klemes,, E. Aizenman,, and G. Glaser. 1998. rexB of bacteriophage lambda is an anti-cell death gene. Proc. Natl. Acad. Sci. USA 95: 15481 15486.
61. Franch, T.,, and K. Gerdes. 2000. U-turns and regulatory RNAs. Curr. Opin. Microbiol. 3: 159 164.
62. Friedberg, E. C.,, G. C. Walker,, and W. Siede. 1995. DNA Repair and Mutagenesis. ASM Press, Washington, D.C..
63. Gabant, P.,, C. Y. Szpirer,, M. Couturier,, and M. Faelen. 1998. Direct selection cloning vectors adapted to the genetic analysis of gram-negative bacteria and their plasmids. Gene 207: 87 92.
64. Gabant, P.,, C. Y. Szpirer,, and L. V. Melderen. 2002. Plasmid poison/antidote systems: functions and technological applications. Recent Research Developments in Plasmid Biology 1: 15 28.
65. Gabant, P.,, T. Van Reeth,, P. L: Dreze,, M. Faelen,, C. Szpirer,, and J. Szpirer. 2000. New positive selection system based on the parD (kis/kid) system of the R1 plasmid. Biotechniques 28: 784 788.
66. Gazit, E.,, and R. T. Sauer. 1999. The Doc toxin and Phd antidote proteins of the bacteriophage PI plasmid addiction system form a heterotrimeric complex. J. Biol Chem. 274: 16813 16818.
67. Gelfand, M. S.,, and E. V. Koonin. 1997. Avoidance of palindromic words in bacterial and archaeal genomes: a close connection with restriction enzymes. Nucleic Acids Res. 25: 2430 2439.
68. Gerdes, K. 2000. Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J. Bacteriol. 182: 561 572.
69. Gerdes, K.,, F. W,. Been,, S. T. Jorgensen,, A. Lobner-Olesen,, P. B. Rasmussen,, T. Atlung,, L. Boe,, O. Karlstrom,, S. Molin,, and K. von Meyenburg. 1986. Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid Rl and its homology with the relF gene product of the E. coli relB operon. EMBO J. 5: 2023 2029.
70. Gerdes, K.,, A. P. Gultyaev,, T. Franch,, K. Pedersen,, and N. D. Mikkelsen. 1997. Antisense RNA-regulated programmed cell death, Annu. Rev. Genet. 31: 1 31.
71. Gerdes, K.,, J. S. Jacobsen,, and T. Franch. 1997. Plasmid stabilization by post-segregational killing. Genet. Eng. 19: 49 451.
72. Gerdes, K.,, P. B. Rasmussen,, and S. Molin. 1986. Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells. Proc. Natl. Acad. Sci. USA 83: 3116 3120.
73. Gong, W.,, M. O'Gara,, R. M. Blumenthal,, and X. Cheng. 1997. Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment. Nucleic Acids Res. 25: 2702 2715.
75. 73a.Gonzalez-Pastor, J, E., E. C. Hobbs, and R. Losick, 2003. Cannibalism by sporulating bacteria. Science 301: 510513.
74. Gotfredsen, M.,, and K. Gerdes. 1998. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol. Microbiol. 29: 1065 1076.
75. Grady, R.,, and F. Hayes. 2003. Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Mol. Microbiol. 47: 1419 1432.
76.Greenfield, T, J., T. Franch, K. Gerdes, and K. E, Weaver. 2001. Antisense RNA regulation of the par post-segregational killing system: structural analysis and mechanism of binding of the antisense RNA, RNAII and its target, RNAI. Mol. Microbiol. 42: 527537.
77. Gronlund, H., and K, Gerdes. 1999. Toxin-antitoxin systems homologous with relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes. J. Mol. Biol. 285: 1401 1415.
78. Gunn, J. S.,, and D. C. Stein. 1997. The Neisseria gonorrhoeae S.NgoVIIl restriction/modification system: a type IIs system homologous to the Haemophilus parahaemolyticus Hphl restriction/modification system. Nucleic Acids Res. 25: 4147 4152.
79. Handa, N.,, A. Ichige,, K. Kusano, and 1. Kobayashi. 2000. Cellular responses to postsegregational killing by restriction-modification genes. J. Bacteriol. 182: 2218 2229.
80. Handa, N., and I, Kobayashi. 2003. Accumulation of large non-circular forms of the chromosome in recombination-defective mutants of Escherichia coli. BMC Mol. Biol. 4: 5.
81.Handa, NM and I. Kobayashi. 1999. Post-segregational killing by restriction modification gene complexes: observations of individual cell deaths. Biochimie 81: 931938.
82. Handa, N.,, Y. Nakayama,, M. Sadykov,, and I. Kobayashi. 2001. Experimental genome evolution: large-scale genome rearrangements associated with resistance to replacement of a chromosomal restriction modification gene complex. Mol. Microbiol. 40: 932 940,
83. Handa, N.,, S. Ohashi,, K. Kusano,, and I. Kobayashi. 1997. X, a x-related 11-mer partially active in an E. coli recC strain. Genes Cells 2: 525 536.
84. Hargreaves, D.,, S. Santos-Sierra,, R. Giraldo,, R. Sabariegos- Jareno,, G. de la Cueva-Mendez,, R. Boelens,, R. Diaz-Orejas,, and J. B. Rafferry. 2002. Structural and functional analysis of the kid toxin protein from E. coli plasmid Rl. Structure ( Cambridge) 10: 1425 1433.
85. Hartley, J. L.,, G. F. Temple,, and M. A. Brasch. 2000. DNA cloning using in vitro site-specific recombination. Genome Res. 10: 1788 1795.
86. Hattman, S.,, J. Wilkinson,, D. Swinton,, S. Schlagman,, P. M. Macdonald,, and G. Mosig. 1985. Common evolutionary origin of the phage T4 dam and host Escherichia colt dam DNAadenine methyltransferase genes. J. Bacteriol. 164: 932 937.
87. Hayes, F. 1998. A family of stability determinants in pathogenic bacteria. J. Bacteriol. 180: 6415 6418.
88. Hazan, R.,, B. Sat,, M. Reches,, and H. Engelberg-Kulka. 2001. Postsegregational killing mediated by the PI phage "addiction module" phd-doc requires the Escherichia coli programmed cell death system mazEF. J. Bacteriol. 183: 2046 2050.
89. Heidelberg, J. F.,, J. A. Eisen,, W. C. Nelson,, R. A. Clayton,, M. L. Gwinn,, R. J. Dodson,, D. H. Haft,, E. K. Hickey,, J. D. Peterson,, L. Umayam,, S. R. Gill,, K. E, Nelson, T. D. Read, H. Tettelin, D. Richardson, M. D. Ermolaeva, J. Vamathevan, S. Bass, H. Qin, I. Dragoi, P. Sellers, L. McDonald, T. Utterback, R. D. Fleishmann, W, C. Nierman, and O. White. 2000. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406: 477 483.
90. Heinemann, J. A.,, and M. W. Silby,. 2003. Horizontal gene transfer and the selection of antibiotic resistance, p. 161 178, In C. F. Amabile-Cuevas (ed.), Multiple Drug Resistant Bacteria. Horizon Scientific Press, Wymondham, United Kingdom.
91. Heitman, J.,, T. Ivanenko,, and A. Kiss. 1999. DNA nicks inflicted by restriction endonucleases are repaired by a RecA-and RecB-dependent pathway in Escherichia coli. Mol. Microbiol. 33: 1141 1151.
92. Hendrix, R. W.,, M. C. Smith,, R. N. Burns, M, E. Ford, and G. F. Hatfull. 1999. Evolutionary relationships among diverse bacteriophages and prophages: all the world's a phage. Proc. Natl. Acad. Sci. USA 96: 2192 2197.
93. Higgins, N. P. 1992. Death and transfiguration among bacteria. Trends Biochem. Sci. 17: 207 211.
94. Hiraga, S.,, A. Jaffe,, T. Ogura,, H. Mori,, and H. Takahashi, 1986. F plasmid ccd mechanism in Escherichia coli. J. Bacteriol. 166: 100 104.
95. Hobbes, T. 1982. Leviathan. Penguin Books, London, United Kingdom.
96.Hurst, G, D., and J. H. Werren. 2001. The role of selfish genetic elements in eukaryotic evolution. Nat. Rev. Genet. 2: 597606.
97. Ibanez, M., I Alvarez, J. M. Rodriguez-Pena, and R. Rotger. 1997. A ColEl-type plasmid from Salmonella enteritidis encodes a DNA cytosine methyltransferase. Gene 196: 145 158.
98. Jacobs, H. T. 1991. Structural similarities between a mitochondrially encoded polypeptide and a family of prokaryotic respiratory toxins involved in plasmid maintenance suggest a novel mechanism for the evolutionary maintenance of mitochondrial DNA. J. Mol Evol. 32: 333 339.
99. Jaffe, A.( T. Ogura, and S. Hiraga. 1985. Effects of the ccd function of the F plasmid on bacterial growth, J . Bacteriol. 163: 841 849.
100. Jamsai, D., M, Nefedov, K. Narayanan, M. Orford, S. Fucharoen, R. Williamson, and P. A. Ioannou. 2003. Insertion of common mutations into the human beta-globin locus using GET recombination and an EcoRl endonuclease counterselection cassette. J. Biotechnol. 101: 1 9.
101. Jeltsch, A.,, M. Kroger,, and A. Pingoud. 1995. Evidence for an evolutionary relationship among type-II restriction endonucleases. Gene 160: 7 16.
102. Jeltsch, A.,, and A. Pingoud. 1996. Horizontal gene transfer contributes to the wide distribution and evolution of type II restriction-modification systems. 7. Mol. Evol. 42: 91 96.
103. Jensen, R. B.,, E. Grohmann,, H. Schwab,, R. Diaz-Orejas,, and K. Gerdes. 1995. Comparison of ccd of F, parDE of RIM, and parD of Rl using a novel conditional replication control system of plasmid Rl. Mol. Microbiol. 17: 211 220.
104. Jiang, Y.,, J. Pogliano,, D. R. Helinski,, and I. Konieczny. 2002. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol. Microbiol. 44: 971 979.
105. Jovanovic, O. S.,, E. K. Ayres,, and D. H. Figurski. 1994. Host-inhibitory functions encoded by promiscuous plasmids. Transient arrest of Escherichia coli segregants that fail to inherit plasmid RK2. J. Mol Biol. 237: 52 64.
106. Kamada, K.,, F. Hanaoka,, and S. K. Burley. 2003. Crystal structure of the Ma/E/MazF complex. Molecular bases of antidote-toxin recognition. Mol. Cell 11: 875 884.
107. Karlin, S.,, A. M. Campbell,, and J. Mrazek. 1998. Comparative DNA analysis across diverse genomes. Annu. Rev. Genet. 32: 185 225.
108. Karoui, H.,, F. Bex,, P. Dreze,, and M. Couturier. 1983. Ham22, a mini-F mutation which is lethal to host cell and promotes recA-dependent induction of lambdoid prophage. EMBO J. 2: 1863 1868.
109. Karyagina, A.,, I. Shilov,, V. Tashlitskii,, M. Khodoun,, S. VasiPev,, P. C. Lau,, and I. Nikolskaya. 1997. Specific binding of sso II DNA methyltransferase to its promoter region provides the regulation of sso II restriction-modification gene expression. Nucleic Acids Res. 25: 2114 2120.
110. Kawano, M.,, T. Oshima,, H. Kasai,, and H. Mori. 2002. Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35- amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli. Mol. Microbiol. 45: 333 349.
111. Kita, K.,, J. Tsuda,, and S. Y. Nakai, 2002. C.EtoOl09I, a regulatory protein for production of EcoOl09l restriction endonuclease, specifically binds to and bends DNA upstream of its translational start site. Nucleic Acids Res. 30: 3558 3565.
112. Kita, K.,, J. Tsuda,, K. Okamoto, H, Yanase, and M. Tanaka. 1999. Evidence of horizontal transfer of the EcoO1091 restriction-modification gene to Escherichia coli chromosomal DNA. J. Bacteriol. 181: 6822 6827.
113. Kleanthous, C.,, R. James,, A. M. Hemmings,, and G. R. Moore. 1999. Protein antibiotics and their inhibitors. Biochem. Soc. Trans. 27: 63 67.
114. Kobayashi, I., Addiction as a principle of symbiosis of genetic elements in the genome—restriction enzymes, chromosome and mitochondria. In M. Sugiura (ed.), Symbiosis and Cellular Organelles. Logos Verlag Berlin, Berlin, Germany, in press.
115. Kobayashi, I. 2001. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution. Nucleic Acids Res. 29: 3742 3756.
116. Kobayashi, I., 1996. DNA modification and restriction: selfish behavior of an epigenetic system, p. 155 172. In V. Russo,, R. Martienssen,, and A. Riggs (ed.), Epigenetic Mechanisms of Gene Regulation. Cold Spring Harbor Laboratory Press, New York, N.Y..
117. Kobayashi, I., 2002. Life cycle of restriction-modification gene complexes, powers in genome evolution, p. 191 200. H. Yoshikawa,, N. Ogasawara,, and N. Satoh (ed,), Genome Science: Towards a New Paradigm? Elsevier, Amsterdam, The Netherlands.
118. Kobayashi, I. 1998. Selfishness and death: raison d'etre of restriction, recombination and mitochondria. Trends Genet. 14: 368 374.
119. Kobayashi, I.,, A. Nobusato,, N. Kobayashi-Takahashi,, and I. Uchiyama. 1999. Shaping the genome—restriction-modification systems as mobile genetic elements. Curr. Opin. Genet. Dev. 9: 649 656.
119a.. Koonin,, E. V.,, A. R. Mushegian,, and P. Bork. 1996. Nonorthologous gene displacement. Trends Genet. 12: 334 336.
120. Krakauer, D. C.,, and J. B. Plotkin. 2002. Redundancy, antiredundancy, and the robustness of genomes. Proc. Natl. Acad. Sci. USA 99: 1405 1409.
121. Kristoffersen, P.,, G. B. Jensen,, K. Gerdes,, and J . Piskur. 2000. Bacterial toxin-antitoxin gene system as containment control in yeast cells. Appl. Environ. Microbiol. 66: 5524 5526.
122. Kroemer, G.,, N. Zamzami,, and S. A. Susin. 1997. Mitochondrial control of apoptosis. Immunol. Today 18: 44 51.
123. Kroger, M.,, E. Blum,, E. Deppe,, A. Dusterhoft,, D. Erdmann,, S. Kilz,, S. Meyer-Rogge,, and D. Mostl. 1995. Organization and gene expression within restriction-modification systems of Herpetosiphon giganteus. Gene 157: 43 47.
124. Kuhar, I.,, J. P. van Putten,, D. Zgur-Bertok,, W. Gaastra,, and B. J. Jordi. 2001. Codon-usage based regulation of colicin K synthesis by the stress alarmone ppGpp. Mol. Microbiol. 41: 207 216.
125.Kuhn. I., F. H. Stephenson, H. W. Boyer, and P. J. Greene. 1986. Positive-selection vectors utilizing lethality of the EcoR1 endonuclease. Gene 42: 253263.
126. Kulakauskas, S.,, A. Lubys,, and S. D. Ehrlich. 1995. DNA restriction-modification systems mediate plasmid maintenance. J. Bacteriol. 177: 3451 3454.
127. Kulik, E. M.,, and T. A. Bickle. 1996. Regulation of the activity of the type IC EcoR1241 restriction enzyme. J. Mol. Biol. 264: 891 906.
128. Kuroda, M.,, T. Ohta,, I. Uchiyama,, T. Baba,, H. Yuzawa,, I. Kobayashi,, L. Cui,, A. Oguchi,, K. Aoki,, Y. Nagai,, J. Lian,, T. Ito,, M. Kanamori,, H. Matsumaru,, A. Maruyama,, H. Murakami,, A. Hosoyama,, Y. Mizutani-Ui,, N. K. Takahashi,, T. Sawano,, R. Inoue,, C. Kaito,, K. Sekimizu,, H. Hirakawa,, S. Kuhara,, S. Goto,, J. Yabuzaki,, M. Kanehisa,, A. Yamashita,, K. Oshima,, K. Furuya,, C. Yoshino,, T. Shiba,, M. Hattori,, N. Ogasawara,, H. Hayashi,, and K. Hiramatsu. 2001. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357: 1225 1240.
129. Kusano, A.,, C. Staber,, H. Y. Chan,, and B. Ganetzky. 2003. Closing the (Ran)GAP on segregation distortion in Drosophila. Bioessays 25: 108 115.
130. Kusano, K.,, T. Naito,, N. Handa,, and I. Kobayashi. 1995. Restriction-modification systems as genomic parasites in competition for specific sequences. Proc. Natl. Acad. Sci. USA 92: 11095 11099.
131. Lawrence, J. G.,, and J. R. Roth. 1996. Selfish operons: horizontal transfer may drive the evolution of gene clusters. Genetics 143: 1843 1860.
132. Lehnherr, H.,, E. Maguin,, S. Jafri,, and M. B. Yarmolinsky. 1993. Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J. Mol. Biol. 233: 414 428.
133. Lehnherr, H.,, and M. B. Yarmolinsky. 1995. Addiction protein Phd of plasmid prophage P1 is a substrate of the CIpXP serine protease of Escherichia coli. Proc. Natl. Acad. Sci. USA 92: 3274 3277.
134. Levin, B. R.,, and J. J. Bull. 1994. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol. 2: 76 81.
135. Lewis, L. K.,, G. R. Harlow,, L. A. Gregg-Jolly,, and D. W. Mount. 1994. Identification of high affinity binding sites for LexA which define new DNA damage-inducible genes in Escherichia coli. J . Mol. Biol. 241: 507 523.
136. Lieb, M. 1991. Spontaneous mutation at a 5-methylcytosine hotspot is prevented by very short patch (VSP) mismatch repair. Genetics 128: 23 27.
137. Lilley, A.,, P. Young,, and M. Bailey,. 2000. Bacterial population genetics: do plasmids maintain bacterial diversity and adaptation?, p. 287 300. In C. M. Thomas (ed.), The Horizontal Gene Pool: Bacterial Plasmids and Gene Spread. Harwood Academic Publishers, Amsterdam, The Netherlands.
138. Lin, L. F.,, J. Posfai,, R. J. Roberts,, and H. Kong. 2001. Comparative genomics of the restriction-modification systems in Helicobacter pylori. Proc. Natl. Acad. Sci. USA 98: 2740 2745.
139. Loris, R.,, M. H. Dao-Thi,, E. M. Bahassi,, L. Van Melderen,, F. Poortmans,, R. Liddington,, M. Couturier,, and L. Wyns. 1999. Crystal structure of CcdB, a topoisomerase poison from E. coli. J. Mol. Biol. 285: 1667 1677.
140. Lubys, A.,, and A. Janulaitis. 1995. Cloning and analysis of the plasmid-borne genes encoding the Bsp61 restriction and modification enzymes. Gene 157: 25 29.
141. Lubys, A.,, S. Jurenaite,, and A. Janulaitis. 1999. Structural organization and regulation of the plasmid-borne type II restriction-modification system Kpn2l from Klebsiella pneumoniae RFL2. Nucleic Acids Res. 27: 4228 4234.
142. Lubys, A.,, J. Lubiene,, S. Kulakauskas,, K. Stankevicius,, A. Timinskas,, and A. Janulaitis. 1996. Cloning and analysis of the genes encoding the type IIS restriction-modification system HphI from Haemophilus parabaemolyticus. Nucleic Acids Res. 24: 2760 2766.
143. Lubys, A.,, S. Menkevicius,, A. Timinskas,, V. Butkus,, and A. Janulaitis. 1994. Cloning and analysis of translational control for genes encoding the Cfr91 restriction-modification system. Gene 141: 85 89.
144. Magnuson, R.,, H. Lehnherr,, G. Mukhopadhyay,, and M. B. Yarmolinsky. 1996. Autoregulation of the plasmid addiction operon of bacteriophage P1. J. Biol. Chem. 271: 18705 18710.
145. Magnuson, R.,, and M. B. Yarmolinsky. 1998. Corepression of the P1 addiction operon by Phd and Doc. J. Bacteriol. 180: 6342 6351.
146. Maki, S.,, S. Takiguchi,, T. Horiuchi,, K. Sekimizu,, and T. Miki. 1996. Partner switching mechanisms in inactivation and rejuvenation of Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA (CcdA). J. Mol. Biol. 256: 473 482.
147. Maki, S.,, S. Takiguchi,, T. Miki,, and T. Horiuchi. 1992. Modulation of DNA supercoiling activity of Escherichia coli DNA gyrase by F plasmid proteins. Antagonistic actions of LetA (CcdA) and LetD (CcdB) proteins. J. Biol. Chem. 267: 12244 12251.
148. Makino, K.,, K. Oshima,, K. Kurokawa,, K. Yokoyama,, T. Uda,, K. Tagomori,, Y. lijima,, M. Najima,, M. Nakano,, and A. Yamashita. 2003. Genome sequence of Vibrio parabaemolyticus: a pathogenic mechanism distinct from that of V. cholerae. Lancet 361: 743 749.
149. Marianovsky, I.,, E. Aizenman,, H. Engelberg-Kulka,, and G. Glaser. 2001. The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome. J. Biol. Chem. 276: 5975 5984.
150. Masuda, Y.,, K. Miyakawa,, Y. Nishimura,, and E. Ohtsubo. 1993. chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R 100. J. Bacteriol. 175: 6850 6856.
151. Masuda, Y.,, and E. Ohtsubo. 1994. Mapping and disruption of the chpB locus in Escherichia coli. J. Bacteriol. 176: 5861 5863.
152. Meinhart, A.,, J. C. Alonso,, N. Strater,, and W. Saengcr. 2003. Crystal structure of the plasmid maintenance system epsilon/ zeta: functional mechanism of toxin zeta and inactivation by epsilon 2 zeta 2 complex formation. Proc. Natl. Acad. Sci. USA 100: 1661 1666.
153. Michel,, B. S. D. Ehrlich,, and M. Uzest. 1997. DNA double-strand breaks caused by replication arrest. EMBO J. 16: 430 438.
154. Miki, T.,, Z. T. Chang,, and T. Horiuchi. 1984. Control of cell division by sex factor F in Escherichia coli II. Identification of genes for inhibitor protein and trigger protein on the 42.84- 43.6 F segment. J. Mol. Biol. 174: 627 646.
155. Miki, T.,, J. A. Park,, K. Nagao,, N. Murayama,, and T. Horiuchi. 1992. Control of segregation of chromosomal DNA by sex factor F in Escherichia coli. Mutants of DNA gyrase subunit A suppress letD (ccdB) product growth inhibition. J. Mol. Biol. 225: 39 52.
156. Miner, Z.,, and S. Hattman. 1988. Molecular cloning, sequencing, and mapping of the bacteriophage T2 dam gene. J. Bacteriol. 170: 5177 5184.
157.Mol, C D. A, S. Arvai, T. J. Begley, R. P. Cunningham, and J. A. Tainer. 2002. Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases. J. Mol. Biol. 315: 373384.
158. Moller-Jensen, J.,, T. Franch, and K, Gerdes. 2001. Temporal translational control by a metastable RNA structure. J. Biol. Chem. 276: 35707 35713.
159. Mongold, J. 1992. Theoretical implications for the evolution of postsegregational killing by bacterial plasmids. Am. Nat. 139: 677 689.
160. Mulec, J.,, Z. Podlesck,, P. Mrak,, A. Kopitar,, A. Ihan,, and D. Zgur-Bertok. 2003. A cka-gfp transcriptional fusion reveals that the colicin K activity gene is induced in only 3 percent of the population. J. Bacteriol. 185: 654 659.
161. Murayama, K.,, P. Orth,, A. B. de la Hoz,, J. C. Alonso,, and W. Saenger. 2001. Crystal structure of omega transcriptional repressor encoded by Streptococcus pyogenes plasmid pSM19035 at 1.5 A resolution. J. Mol. Biol. 314: 789 796.
162. Naas, T.,, M. Blot,, W. M. Fitch,, and W. Arber. 1995. Dynamics of IS-related genetic rearrangements in resting Escherichia coli K-12. Mol. Biol. Evol. 12: 198 207.
163. Nagel, J. H.,, A. P. Gultyaev,, K. J. Oistamo,, K. Gerdes, and C W. Pleij. 2002. A pH-jump approach for investigating secondary structure refolding kinetics in RNA, Nucleic Acids Res. 30: e63.
164. Naito, T.,, K. Kusano,, and I. Kobayashi. 1995. Selfish behavior of restriction-modification systems. Science 267: 897 899,
165. Nakamaru, M.,, and Y. Iwasa. 2000. Competition by allelopathy proceeds in traveling waves: colicin-immune strain aids colicin-sensitive strain. Theor. Popul. BioL 57: 131 144.
166. Nakayama, Y.,, and I. Kobayashi. 1998. Restriction-modification gene complexes as selfish gene entities: roles of a regulatory system in their establishment, maintenance, and apoptotic mutual exclusion. Proc. Nat. Acad. Sci. USA 95: 6442 6447.
167. Nielsen, A. K.,, and K. Gerdes. 1995. Mechanism of post-segregational killing by hok-homologue pnd of plasmid R483: two translational control elements in the pnd mRNA. J. Mol. Biol. 249: 270 282.
168. Nielsen, A. K.,, P. Thorsted,. T. Thisted,, E. G. Wagner,, and K. Gerdes. 1991. The rifampicin-induciblc genes srnB from F and pnd from R483 are regulated by antisense RNAs and mediate plasmid maintenance by killing of plasmid-free segregants. Mol. Microbiol. 5: 1961 1973.
169. Nitta, T.,, H. Nagamitsu,, M. Murata,, H. Izu,, and M. Yamada. 2000. Function of the sigma(E) regulon in dead-cell lysis in stationary-phase Escherichia coli. J. Bacteriol. 182: 5231 5237.
170. Nobusato, A., 1. Uchiyama, and I. Kobayashi. 2000. Diversity of restriction-modification gene homologues in Helicobacter pylori. Gene 259: 89 98.
171. Nobusato, A.,, I. Uchiyama,, S. Ohashi,, and I. Kobayashi. 2000. Insertion with long target duplication: a mechanism for gene mobility suggested from comparison of two related bacterial genomes. Gene 259: 99 108,
172. Nolling, J.,, and W. M. de Vos. 1992. Characterization of the archaeal, plasmid-encoded type II restriction-modification system MthTI from Methanobacterium thermoformicicum THF: homology to the bacterial NgoPII system from Neisseria gonorrhoeae. J. Bacteriol. 174: 5719 5726.
173. Nolling, J.,, F. J. van Eeden,, R. I. Eggen,, and W. M. de Vos. 1992. Modular organization of related archaeal plasmids encoding different restriction-modification systems in Methanobacterium thermoformicicum. Nucleic Acids Res. 20: 6501 6507.
174. Oberer, M.,, K. Zangger,, S. Prytulla,, and W. Keller. 2002. The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins. Biochem. J. 361: 41 47.
175. O'Connor, C. D.,, and G. O. Humphreys. 1982. Expression of the EcoRl restriction-modification system and the construction of positive-selection cloning vectors. Gene 20: 219 229.
176. Ogura, T.,, and S. Hiraga. 1983. Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc. Natl. Acad. Sci. USA 80: 4784 4788.
177. Ohnishi, Y.,, H. Iguma,, T. Ono,, H. Nagaishi,, and A. J. Clark. 1977. Genetic mapping of the F plasmid gene that promotes degradation of stable ribonucleic acid in Escherichia coli. J. Bacteriol. 132: 784 789.
178. Ohshima, H.,, S. Matsuoka,, K. Asai,, and Y. Sadaie. 2002. Molecular organization of intrinsic restriction and modification genes BsuM of Bacillus subtilis Marburg, J . Bacteriol. 184: 381 389.
179. O'Neill, M.,, A. Chen,, and N. E. Murray. 1997. The restriction- modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities. Proc. Natl. Acad. Sci. USA 94: 14596 14601.
180. Ono, T.,, S. Akimoto,, K. Ono,, and Y. Ohnishi. 1986. Plasmid genes increase membrane permeability in Escherichia coli. Biochim. Biophys. Acta 867: 81 88.
181. O'Sullivan, D. J.,, and T. R. Klaenhammer. 1998. Control of expression of Llal restriction in Lactococcus lactis. Mol. Microbiol. 27: 1009 1020.
182. O'Sullivan, D.J.,, K. Zagula,.and T. R. Klaenhammer. 1995. In vivo restriction by Llal is encoded by three genes, arranged in an operon with llalM, on the conjugative Lactococcus plasmid pTR2030. J. Bacteriol. 177: 134 143.
183. Palmer, B. R.,, and M. G. Marinus. 1994. The dam and dcm strains of Escherichia coli—a review. Gene 143: 1 12.
184. Pecota, D. C., C. S. Kim,, K. Wu,, K. Gerdes,, and T. K. Wood. 1997. Combining the hok/sok, parDE, and pnd postsegregational killer loci to enhance plasmid stability. Appl. Environ. Microbiol. 63: 1917 1924.
185. Pecota, D. C.,, and T. K. Wood. 1996. Exclusion of T4 phage by the hoklsok killer locus from plasmid R1. J. Bacteriol. 178: 2044 2050.
186. Pedersen, K.,, S. K. Christenscn,, and K. Gerdes. 2002. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol. Microbiol. 45: 501 510.
187. Pedersen, K.,, and K. Gerdes. 1999. Multiple hok genes on the chromosome of Escherichia coli. Mol. Microbiol. 32: 1090 1102.
188. Pedersen, K.,, A. V. Zavialov. M. Y. Pavlov, J. Elf, K. Gerdes, and M. Ehrenberg. 2003. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112: 131 140.
189. Penner, M.,, I. Morad,, L. Snyder,, and G. Kaufmann. 1995. Phage T4-coded Stp: double-edged effector of coupled DNA and tRNA-restriction systems. J Mol. Biol. 249: 857 868.
190. Perna, N. T.,, G. Plunkett, 3rd, V. Burland, B. Mau, J. D. Glasner, D. J. Rose, G. F. Mayhew, P. S. Evans, J. Gregor, H. A. Kirkpatrick, G. Posfai, J. Hackett, S. Klink, A. Boutin, Y. Shao, L. Miller, E. J. Grotbeck, N. W. Davis, A. Lim, E. T. Dimalanta, K. D. Potamousis, J. Apodaca, T. S. Anantharaman, J. Lin, G. Yen, D. C. Schwartz, R. A, Welch, and F. R. Blattner. 2001. Genome sequence of enterohaemorrhagic Escherichia coli 0157:117. Nature 409: 529 533.
191. Pingoud, A.,, and A. Jeltsch. 2001. Structure and function of type II restriction endonucleases. Nucleic Acids Res. 29: 3705 3727.
192. Prakash-Cheng, A.,, and J. Ryu. 1993. Delayed expression of in vivo restriction activity following conjugal transfer of Escherichia coli hsdK (restriction-modification) genes. J. Bacteriol 175: 4905 1906.
193. Price, C.,, J. Lingner,, T. A. Bickle,, K. Firman,, and S. W. Glover. 1989. Basis for changes in DNA recognition by the EeoR124 and EcoR124/3 type I DNA restriction and modification enzymes. J. Mol Biol 205: 115 125.
194. Ravagnan, L.,, T. Roumier,, and G. Kroemer. 2002. Mitochondria, the killer organelles and their weapons. J. Cell Physiol 192: 131 137.
195. Rawlings, D. E. 1999. Proteic toxin-antitoxin, bacterial plasmid addiction systems and their evolution with special reference to the pas system of pTF-FC2. FEMS Microbiol. Lett. 176: 269 277.
196. Rimseliene, R.,, R. Vaisvila,, and A. Janulaitis. 1995. The ero72IC gene specifies a trans-acting factor which influences expression of both DNA methyltransferase and endonuclease from the Eco72I restriction-modification system. Gene 157: 217 219.
197. Roberts, R. C, A. R, Strom, and D. R. Helinski. 1994. The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss. J. Mol. Biol. 237: 35 51.
198. Roberts, R. J.,, M. Belfort,, T. Bestor,, A. S. Bhagwat,, T. A. Bickle,, J. Bitinaite,, R. M. Blumenthal,, S. Degtyarev,, D. T. Dryden,, K. Dybvig,, K. Firman,, E. S. Gromova,, R. I. Gumport,, S. E. Halford,, S. Hattman,, J. Hcitman,, D. P. Hornby,, A. Janulaitis,, A. Jeltsch,, J. Josephsen,, A. Kiss,, T. R. Klaenhammer,, I. Kobayashi,, H. Kong,, D. H. Kruger,, S. Lacks,, M. G. Marinus,. M. Miyahara,, R. D. Morgan,, N. E. Murray,, V. Nagaraja,, A. Piekarowicz,, A. Pingoud,, E. Raleigh,, D. N. Rao,, N. Reich,, V. E. Repin,, E. U. Selker,, P. C. Shaw,, D. C. Stein,, B. L. Stoddard,, W. Szybalski,, T. A. Trautner,, J. L. Van Etten,, J. M. Vitor,, G. G. Wilson,, and S. Y. Xu. 2003. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res. 31: 1805 1812.
199. Roberts, R. J.,, T. Vincze,, J. Posfai,, and D. Macelis. 2003. REBASE: restriction enzymes and methyltransferases. Nucleic Acids Res. 31: 418 420.
200. Rocha, E. P.,, A. Danchin,, and A. Viari. 2001. Evolutionary role of restriction/modification systems as revealed by comparative genome analysis. Genome Res. 11: 946 958.
201. Rocha, E. P.,, A. Viari,, and A. Danchin. 1998. Oligonucleotide bias in Bacillus subtilis: general trends and taxonomic comparisons. Nucleic Acids Res. 26: 2971 2980.
202. Rochepeau, P.,, L. B. Selinger,, and M. F. Hynes. 1997. Transposon-like structure of a new plasmid-encoded restriction-modification system in Rhizobium leguminosarum VF39SM. Mol. Gen. Genet. 256: 387 396.
203. Rosche, T. M.,, A. Siddique,, M. H. Larsen,, and D. H. Figurski. 2000. Incompatibility protein IncC and global regulator KorB interact in active partition of promiscuous plasmid RK2. J. Bacteriol. 182: 6014 6026.
204. Rowe-Magnus, D. A.,, A.-M. Guerout,, L. Biskri,, P. Bouige,, and D. Mazel. 2003. Comparative analysis of superintegrons: engineering extensive genetic diversity in the Vibrionaceae. Genome Res. 13: 428 442.
205. Rowe-Magnus, D. A.,, A.-M. Guerout, P, Ploncard, B, Dychinco, J. Davies, and D. Mazel. 2001. The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons. Proc. Natl. Acad. Sci. USA 98: 652 657.
206. Ruiz-Echcvarria, M. J.,, A. Berzal-Herranz,, K. Gerdes,, and R. Diaz-Orejas. 1991. The kis and kid genes of the parD maintenance system of plasmid Rl form an operon that is autoregulated at the level of transcription by the co-ordinated action of the Kis and Kid proteins. Mol. Microbiol 5: 2685 2693.
207. Ruiz-Echcvarria, M. J.,, G. de la Cueva,, and R. Diaz-Orejas. 1995. Translational coupling and limited degradation of a polycistronic messenger modulate differential gene expression in the parD stability system of plasmid Rl. Mol. Gen. Genet. 248: 599 609.
208. Ruiz-Echevarria, M. J.,, G. de Torrontegui,, G. Gimenez- Gallego,, and R. Diaz-Orejas. 1991. Structural and functional comparison between the stability systems ParD of plasmid Rl and Ccd of plasmid F. Mol. Gen. Genet. 225: 355 362.
209. Ruiz-Echevarria, M. J.,, G. Gimenez-Gallego,, R. Sabariegos- Jareno,, and R. Diaz-Orejas. 1995. Kid, a small protein of the parD stability system of plasmid Rl, is an inhibitor of DNA replication acting at the initiation of DNA synthesis. J. Mol. Biol. 247: 568 577.
210. Sadykov, M.,, Y. Asami,, H. Niki,, N. Handa,, M. Itaya,, M. Tanokura,, and I. Kobayashi. 2003. Multiplication of a restriction-modification gene complex. Mol. Microbiol 48: 417 427.
211. Sadykov, M.,, Y. Asami,, H. Niki,, N. Handa,, M. haya,, M. Tanokura,, and I. Kobayashi. 2003. Multiplication of a restriction modification gene complex. Mol. Microbiol. 48: 417 427.
212. Sampath, J.,, and M. N. Vijayakumar. 1998. Identification of a DNA cytosine methyltransferase gene in conjugative transposon Tn5252. Plasmid 39: 63 76.
213. SanMiguel, P.,, A. Tikhonov,, Y. K. Jin,, N. Motchoulskaia,, D. Zakharov,, A. Melake-Berhan,, P. S. Springer,, K. J. Edwards,, M. Lee,, Z. Avramova,, and J. L. Bennetzen. 1996. Nested retrotransposons in the intergenic regions of the maize genome. Science 274: 765 768.
214. Santos Sierra, S.,, R. Giraldo,, and R. Diaz Orcjas. 1998. Functional interactions between cbpB and parD, two homologous conditional killer systems found in the Escherichia coli chromosome and in plasmid Rl . FEMS Microbiol. Lett. 168: 51 58.
215. Santos-Sierra, S.,, R. Giraldo,, and R. Diaz-Orejas. 1997. Functional interactions between homologous conditional killer systems of plasmid and chromosomal origin. FEMS Microbiol Lett. 152: 51 56.
216. Sat, B.,, R. Hazan,, T. Fisher,, H. Khaner,, G. Glaser,, and H. Engelberg-Kulka. 2001. Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J. Bacteriol. 183: 2041 2045.
217. Sat, B.,, M. Reches,, and H. Engelberg-Kulka. 2003. The Escherichia coli mazEF suicide module mediates thymineless death. J. Bacteriol 185: 1803 1807.
218.Saunders, N, J., J. F. Peden, D. W. Hood, and E. R. Moxon. 1998. Simple sequence repeats in the Helicobacter pylori genome. Mol. Microbiol 27: 10911098.
219. Saunders, N. J . , and L. A. S. Snyder. 2002. The minimal mobile element. Microbiology 148: 3756 3760.
220. Sayeed, S.,, L. Reaves,, L. Radnedge,, and S. Austin. 2000. The stability region of the large virulence plasmid of Shigella flexneri encodes an efficient postsegregational killing system. J. Bacteriol. 182: 2416 2421.
221. Sekizaki, T.,, Y. Otani,, M. Osaki,, D. Takamatsu,, and Y. Shimoji. 2001. Evidence for horizontal transfer of SsuDATI I restriction-modification genes to the Streptococcus suis genome. Bacteriol. 183: 500 511.
222. Sergueev, K.,, D. Court,, L. Reaves,, and S. Austin. 2002. E. coli cell-cycle regulation by bacteriophage lambda. J. Mol Biol 324: 297 307.
223. Sergueev, K.,, D. Yu,, S. Austin,, and D. Court. 2001. Cell toxicity caused by products of the p(L) operon of bacteriophage lambda. Gene 272: 227 235.
224. Slavcev, R. A.,, and S. Hayes. 2003. Stationary phase-like properties of the bacteriophage lambda Rex exclusion phenotype. Mol. Genet. Genomics 269: 40 48.
225. Smith, A. S.,, and D. E. Rawlings. 1998. Autoregulation of the pTF-FC2 proteic poison-antidote plasmid addiction system (pas) is essential for plasmid stabilization. J. Bacteriol. 180: 5463 5465.
226. Smith, A. S.,, and D. E. Rawlings. 1998. Efficiency of the pTF-FC2 pas poison-antidote stability system in Escherichia coli is affected by the host strain, and antidote degradation requires the Ion protease. J. Bacteriol. 180: 5458 5462.
227. Smith, A. S., and D, E. Rawlings. 1997. The poison-antidote stability system of the broad-host-range Thiohacillus ferrooxidans plasmid pTF-FC2. Mol. Microbiol. 26: 961 970.
228. Snyder, L. 1995. Phage-exclusion enzymes: a bonanza of biochemical and cell biology reagents? Mol. Microbiol. 15: 415 420.
229. Som, S.,, and S. Friedman. 1993. Autogenous regulation of the EcoRII methylase gene at the transcriptional level: effect of 5-azacytidine. EMBO J. 12: 4297 4303.
230. Som, S.,, and S. Friedman. 1997. Characterization of the intcrgenic region which regulates the Mspl restriction-modification system. J. Bacteriol. 179: 964 967,
231. Sonoda, E.,, M. S. Sasaki,, J.-M. Buersteddc,, O. Bezzubova,, A. Shinohara,, H. Ogawa,, M. Takata,, Y. Yamaguchi-Iwai,, and S. Takeda. 1998. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J. 17: 598 608.
232. Stein, D. C.,, J. S. Gunn,, and A. Piekarowiez. 1998. Sequence similarities between the genes encoding the S.Ngol and Haell restriction/modification systems. Biol. Chem. 379: 575 578.
233. Summers, D. K. 1996. The Biology of Plasmids. Blackwell Publishing Ltd., Oxford, United Kingdom.
234. Syvanen, M.,, and C. I. Kado (ed.). 2002. Horizontal Gene Transfer, 2nd ed. Academic Press, London, United Kingdom.
235. Takahashi, N.,, and I. Kobayashi. 1990. Evidence for the double-strand break repair model of bacteriophage 1 recombination. Proc. Natl. Acad. Sci. USA 87: 2790 2794.
236. Takahashi, N.,, Y. Naito,, N. Handa,, and I. Kobayashi. 2002. A DNA methyltransferase can protect the genome from postdisturbance attack by a restriction-modification gene complex. J. Bacteriol. 184: 6100 6108.
237. Tarn, J. E.,, and B. C. Kline. 1989. The F plasmid ccd autorepressor is a complex of CcdA and CcdB proteins. Mol. Gen. Genet. 219: 26 32.
238. Tao, T.,, J. C. Bourne,, and R. M. Blumenthal. 1991. A family of regulatory genes associated with type II restriction-modification systems. J. Bacteriol. 173: 1367 1375.
239. Teodoro, J. G.,, and P. E. Branton. 1997. Regulation of apoptosis by viral gene products. J. Virol. 71: 1739 1746.
240. Terawaki, Y.,, Y. Kakizawa,, H. Takayasu,, and M. Yoshikawa. 1968. Temperature sensitivity of cell growth in Escherichia coli associated with the temperature sensitive R(fCM) factor. Nature 219: 284 285.
241. Thomas, C. M. (ed.). 2000. The Horizontal Gene Pool: Bacterial Plasmids and Gene Spread. Harwood Academic Publishers, Amsterdam, The Netherlands.
242. Tian, Q. B.,, T. Hayashi,, T. Murata,, and Y. Terawaki. 1996. Gene product identification and promoter analysis of big locus of plasmid Rtsl. Biocbem. Biopbys. Res. Commun. 225: 679 684.
243. Tian, Q. B.,, M. Ohnishi,, T. Murata,, K. Nakayama,, Y. Terawaki,, and T. Hayashi. 2001. Specific protein-DNA and protein-protein interaction in the hig gene system, a plasmid-borne proteic killer gene system of plasmid Rts I. Plasmid 45: 63 74.
244. Tian, Q. B.,, M. Ohnishi,, A. Tabuchi,, and Y. Terawaki. 1996. A new plasmid-encoded proteic killer gene system: cloning, sequencing, and analyzing hig locus of plasmid Rtsl. Biocbem. Biopbys. Res. Commun. 220: 280 284.
245. Torres, B.,, S. Jaeneckc,, K. N. Timmis,, J. L. Garcia,, and E. Diaz. 2000. A gene containment strategy based on a restriction- modification system. Environ. Microbiol. 2: 555 563.
246. Trautner, T. A.,, and M. Noyer-Weidner,. 1993. Restriction/ modification and methylase systems in Bacillus subtilis, related species, and their phages, p. 539 552. In A. L. Sonenshcin,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics. American Society for Microbiology, Washington, D.C..
247. Tsuchimoto, S.,, Y. Nishimura,, and E. Ohtsubo. 1992. The stable maintenance system pent of plasmid R100: degradation of Peml protein may allow PcmK protein to inhibit cell growth. J. Bacteriol. 174: 4205 1211.
248. Tsuchimoto, S.,, and E. Ohtsubo. 1993. Autoregulation by cooperative binding of the Peml and PcmK proteins to the promoter region of the pew operon. Mol. Gen. Genet. 237: 81 88.
249. Tsuchimoto, S.,,and E. Ohtsubo. 1989. Effect of the pent system on stable maintenance of plasmid R100 in various Escherichia coli hosts. Mol. Gen. Genet. 215: 463 468.
250. Tsuchimoto, S.,, H. Ohtsubo,, and E. Ohtsubo. 1988. Two genes, pemK and peml, responsible for stable maintenance of resistance plasmid R 100. J. Bacteriol. 170: 1461 1466.
251. Twomey, D. P.,, L. L. McKay,, and D. J. O'Sullivan. 1998. Molecular characterization of the Lactococctts lactis LlaKR2I restriction-modification system and effect of an IS982 element positioned between the restriction and modification genes, J. Bacteriol 180: 5844 5854.
252. Tyndall, C.,, H. Lehnherr,, U. Sandmeier,, E. Kulik,, and T. A. Bickle. 1997. The type IC bsd loci of the enterobacteria are flanked by DNA with high homology to the phage PI genome: implications for the evolution and spread of DNA restriction systems. Mol. Microbiol. 23: 729 736.
253. Vaisvila, R.,, G. Vilkaitis,, and A. Janulaitis. 1995. Identification of a gene encoding a DNA invertase-likc enzyme adjacent to the PaeR71 restriction-modification system. Gene 157: 81 84.
254. Van Melderen, L.,, P. Bernard,, and M. Couturier, 1994. Lon-dependent proteolysis of CxrdA is the key control for activation of CcdB in plasmid-free segregant bacteria. Mol Microbiol. 11: 1151 1157.
255. Van Melderen, L.,, M. Thi,, P. Lecchi,, S. Gottesman,, M. Couturier,, and M. R. Maurizi. 1996. ATP-dependent degradation of CcdA by Lou protease. Effects of secondary structure and heterologous subunit interactions. J. Biol. Chem. 271: 27730 27738.
256. Vijesurier, R. M.,, L. Carlock,, R. M. Blumenthal,, and J. C. Dunbar. 2000 , Role and mechanism of action of C. Pvull, a regulatory protein conserved among restriction-modification systems. J. Bacteriol. 182: 477 487.
257. Wagner, E. G.,, S. Altuvia,, and P. Romby. 2002. Antisense RNAs in bacteria and their genetic elements. Adv. Genet. 46: 361 398.