1887

Chapter 19 : DNA Recombination Strategies During Antigenic Variation in the African Trypanosome

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

Preview this chapter:
Zoom in
Zoomout

DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap19-1.gif /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap19-2.gif

Abstract:

One of the most powerful drivers of evolutionary change is the process of adaptation and counter-adaptation by interacting species ( ). The so-called “arms race” between parasites and their hosts is a prime example of such reciprocal coevolution: host adaptations that reduce or attempt to remove parasites select for parasite adaptations that enable evasion of host defences. Elaborate, powerful and sometimes elegant mechanisms of host immunity and parasite infectivity are thought to have arisen from many iterations of this process. A case in point is the mammalian adaptive immune system, perhaps one of the more complex host defence mechanisms detailed to date, which uses directed DNA rearrangements, mutagenesis and selection during the development of T and B immune cells to generate vast numbers of genes encoding immunoglobulin receptors capable of recognizing the huge range of antigens in infecting pathogens ( ). Parasites, on the other hand, have evolved various means of evading adaptive immunity. One such mechanism of immune evasion that is widely recorded among viruses and bacterial and eukaryotic pathogens is antigenic variation. Because parasite killing often depends on a match between circulating host immunity and parasite antigen, individual parasites that no longer express that antigen variant, but instead express an antigenically different variant in its place, survive and can proliferate. However, this advantage tends to be short-lived because immune responses will develop against the different antigen in turn. Hence, members of parasite lineages inhabiting an immunocompetent host are repeatedly being selected for antigenic novelty over the course of infection.

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Architecture and singular transcription of variant surface glycoprotein () gene expression sites in . The four line diagrams show cartoon representations of telomeric expression sites. The top diagram shows a generic bloodstream expression site (BES), while the two diagrams below display examples of variant BES ( ) in which pseudogenes (ψ, peach box) are found (BES 14) or where there has been loss of several expression site associated genes (s; dark blue box) or pseudogenes (light blue box) (BES 10). The final line diagram shows a expression site (MES) used in metacyclic form , which are found in the tsetse; here, the RNA polymerase I (Pol I) promoter (flag) does not drive expression of ESAGs, as it does in the BES, but only the (red box), which in all cases is found adjacent to the telomere (telo; vertical line). Upstream of the MES promoter, several pseudogenes have been described, suggesting that these sites were derived from the BES. Arrays of 70-bp DNA repeats in the BES and MES are shown (hatched box), which always appear to be upstream of genes or pseudogenes. Only one BES or MES is actively transcribed at a time in a single cell. A bloodstream form cell is shown, in which the nucleus is diagrammed. The single active BES (red, extended arrow denotes transcription) is shown associated with the expression site body (ESB, small green circle), which is spatially distinct from the nucleolus (large green circle), though both subnuclear structures are sites of RNA Pol I transcription. Silent BES (three are shown in black; truncated arrow denotes limited transcription) do not associate with the ESB or nucleolus.

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

The variant surface glycoprotein () gene archive in . Whole chromosomes are shown separated by pulsed field gel electrophoresis and stained with ethidium bromide. To the left of the gel, the positions of the megabase chromosomes, intermediate chromosomes and minichromosomes that comprise the nuclear genome are indicated, including the size and number of the different chromosome classes. To the right of the gel, the different loci in which s are found are indicated (bloodstream expression site (BES), mini, array), including the number of s in each locus type and whether they are functional (intact, red box) or are pseudogenic (ψ, peach box). BES denotes s in expression sites that are used in the mammalian bloodstream and are found in the megabase and intermediate chromosomes. Mini denotes s found in the minichromosomes, and array denotes s found in the subtelomeres of the megabase chromosomes. In each case the presence or absence of a number of sequence features in addition to the is shown: the telomere (vertical line), 70-bp repeats (widely hatched box), expression site-associated genes (black box), the RNA Pol I promoter (arrow) and 177-bp repeats (narrow hatched box).

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Hierarchy of variant surface glycoprotein () gene switching by recombination during infections by . The graph depicts the log of the number of cells in a cow up to 70 days after infection (day 0). The schematic below details the timing of activation, by switching, of the different found in the genome ( type): silent telomeric s (telomere) are activated more frequently than intact, subtelomeric array s (array), which in turn are activated more frequently than pseudogenes (pseudo). Gene conversion is the most frequent route for the above activation events, and the features associated with gene conversion of each type are diagrammed. The expressed before a switch (blue box) is transcribed (dotted arrow) from a bloodstream expression site (BES), in which the is adjacent to the telomere (vertical line) and flanked upstream by 70-bp repeats (hatched box) and expression site associated genes (s; black boxes). The amount of sequence copied during gene conversion is shown. For telomeric s the sequence copied normally encompasses the open reading frame (red box) and extends upstream to the 70-bp repeats, but also can extend further upstream into the s if the silent is in an inactive BES; the downstream conversion limit may be the end of the , but can also extend to the telomere from either a minichromosome or inactive BES. Gene conversion of an intact subtelomeric array is more limited in the range of sequence copied. In segmental gene conversion parts of multiple, normally nonfunctional pseudogenes (orange, red or brown boxes) are combined to generate a novel mosaic ; though this is shown to occur in the BES, it is not known if this is the location of gene assembly. Note also, the pseudogene donors are shown for convenience as a contiguous array; in fact, segmental gene conversions using adjacent genes have never been observed.

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Complexity of variant surface glycoprotein () mosaics formed by segmental gene conversion in . (A) Where the 3′ boundary of segmental gene conversion occurs within the coding sequence of the (3′ donation), part or all of the previously expressed C-terminal-domain-(CTD) -encoding region of is retained, allowing the expression of a large contingent of silent s (red box) that contain frameshifts or stop codons towards their 3′ ends (frameshift or premature stop codon indicated by an asterisk); as in Fig. 3 , the recipient (blue) is shown in the bloodstream expression site (BES) and the extent of conversion is indicated (NTD denotes N-terminal domain). Donors of s formed in this way were found to share little sequence similarity over their whole sequence. (B) Mosaic s can allow (partial) expression of pseudogene s. Donors of s (pink box) formed in this way share relatively high levels of sequence similarity (73% identity at the nucleotide level). (C) Segmental gene conversion yields diverse products: the diagram shows nine different s detected during chronic infections ( ); different donors are indicated in different colours, with 3′ donors indicated by hatching.

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Models for variant surface glycoprotein () recombination during antigenic variation in . (A) Recombination is shown initiated by a DNA double-strand break (DSB) in the 70 bp repeats (hatched box) upstream of the (black arrow) in the bloodstream expression site (BES) (s and promoter are not shown). Only factors that have been examined for a role in switching are indicated; those shown in color have been found to act, while those for whom no evidence of a role in switching has been found are shown in gray. DSB processing to reveal 3′ single-stranded ends is, in part, catalyzed by MRE11-RAD50-XRS2/NBS1 (MRX), generating a substrate on which RAD51 forms a nucleoprotein filament; note, however, that a further exonuclease (not shown) normally acts with MRX of both ends of the DSB are processed. RAD51 function is mediated by a number of factors: BRCA2 influences RAD51 filament dynamics, while the detailed roles of RAD51 paralogs (RAD51-3, RAD51-4, RAD51-5 and RAD51-6 in ) are unclear. RAD51 catalyzes repair by homology-dependent invasion of the single-stranded end into intact DNA (gray lines), containing a silent (gray arrow). Mismatch repair constrains homologous recombination to act only on sufficiently homologous sequences. Three pathways for DSB repair have been described and may contribute to switching. (B) DSB repair; here, newly synthesized DNA is copied from the intact DNA duplex and remains base-paired, generating Holliday junction structures whose enzymatic resolution can lead to gene conversion with (not shown) or without (shown) crossover of flanking sequence. In , RMI1-TOP3 has been shown to suppress crossover, by perhaps acting on the Holliday junctions. (C) Synthesis-dependent strand annealing; here, newly synthesized DNA is displaced from the intact duplex and reanneals with homologous sequence at the DSB, allowing synthesis of the other strand. Break-induced replication is shown in (D); in this mechanism, an origin-independent replication fork forms on the strand invasion intermediate allowing replication to the chromosome end.

Citation: McCulloch R, Morrison L, Hall J. 2015. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome, p 409-435. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0016-2014
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555819217.chap19
1. Brockhurst MA,, Koskella B . 2013. Experimental coevolution of species interactions. Trends Ecol Evol 28 : 367 375.[PubMed] [CrossRef]
2. Hirano M,, Das S,, Guo P,, Cooper MD . 2011. The evolution of adaptive immunity in vertebrates. Adv Immunol 109 : 125 157.[PubMed] [CrossRef]
3. Sniegowski PD,, Murphy HA . 2006. Evolvability. Curr Biol 16 : R831 R834.[PubMed] [CrossRef]
4. Graves CJ,, Ros VI,, Stevenson B,, Sniegowski PD,, Brisson D . 2013. Natural selection promotes antigenic evolvability. PLoS Pathog 9 : e1003766. [PubMed] [CrossRef]
5. Nuismer SL,, Otto SP . 2005. Host–parasite interactions and the evolution of gene expression. PLoS Biol 3 : e203. [PubMed] [CrossRef]
6. Gjini E,, Haydon DT,, Barry JD,, Cobbold CA . 2010. Critical interplay between parasite differentiation, host immunity, and antigenic variation in trypanosome infections. Am Nat 176 : 424 439.[PubMed] [CrossRef]
7. Borst P, . 2002. Antigenic Variation in Eukaryotic Parasites, p 953 971. In Craig NL,, Berg DE (ed), Mobile DNA II. ASM Press, Washington.
8. Barry JD,, McCulloch R . 2001. Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol 49 : 1 70.[PubMed] [CrossRef]
9. Deitsch KW,, Moxon ER,, Wellems TE . 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol Mol Biol Rev 61 : 281 293.[PubMed]
10. Deitsch KW,, Lukehart SA,, Stringer JR . 2009. Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat Rev Microbiol 7 : 493 503.[PubMed] [CrossRef]
11. Turner CM . 1997. The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei . FEMS Microbiol Lett, 153 : 227 231.[PubMed] [CrossRef]
12. Norris SJ . 2006. Antigenic variation with a twist—the Borrelia story. Mol Microbiol 60 : 1319 1322.[PubMed] [CrossRef]
13. Barrett MP,, Burchmore RJ,, Stich A,, Lazzari JO,, Frasch AC,, Cazzulo JJ,, Krishna S . 2003. The trypanosomiases. Lancet 362 : 1469 1480.[PubMed] [CrossRef]
14. Lai DH,, Hashimi H,, Lun ZR,, Ayala FJ,, Lukes J . 2008. Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei . Proc Natl Acad Sci USA 105 : 1999 2004.[PubMed] [CrossRef]
15. Barbet AF,, McGuire TC . 1978. Crossreacting determinants in variant-specific surface antigens of African trypanosomes. Proc Natl Acad Sci USA 75 : 1989 1993.[PubMed] [CrossRef]
16. Barry JD . 1986. Antigenic variation during Trypanosoma vivax infections of different host species. Parasitology 92 : 51 65.[PubMed] [CrossRef]
17. Vickerman K . 1978. Antigenic variation in trypanosomes. Nature 273 : 613 617.[PubMed] [CrossRef]
18. Vickerman K,, Luckins AG . 1969. Localization of variable antigens in the surface coat of Trypanosoma brucei using ferritin conjugated antibody. Nature 224 : 1125 1126.[PubMed] [CrossRef]
19. Cross GA . 1975. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei . Parasitology 71 : 393 417.[PubMed] [CrossRef]
20. Borst P,, Cross GA . 1982. Molecular basis for trypanosome antigenic variation. Cell 29 : 291 303.[PubMed] [CrossRef]
21. Morrison LJ,, Marcello L,, McCulloch R . 2009. Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity. Cell Microbiol 11 : 1724 1734.[PubMed] [CrossRef]
22. Horn D . 2009. Antigenic variation: extending the reach of telomeric silencing. Curr Biol 19 : R496 R498.[PubMed] [CrossRef]
23. Rudenko G . 2011. African trypanosomes: the genome and adaptations for immune evasion. Essays Biochem 51 : 47 62.[PubMed]
24. Horn D,, McCulloch R . 2010. Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Curr Opin Microbiol 13 : 700 705.[PubMed] [CrossRef]
25. Glover L,, Hutchinson S,, Alsford S,, McCulloch R,, Field MC,, Horn D . 2013. Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control. Cell Microbiol 15 : 1984 1993.[PubMed] [CrossRef]
26. Higgins MK,, Carrington M . 2014. Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families. Protein Sci 23 : 354 365.[PubMed] [CrossRef]
27. Barry JD,, Hall JP,, Plenderleith L . 2012. Genome hyperevolution and the success of a parasite. Ann NY Acad Sci 1267 : 11 17.[PubMed] [CrossRef]
28. Barbour AG,, Restrepo BI . 2000. Antigenic variation in vector-borne pathogens. Emerg Infect Dis 6 : 449 457.[PubMed] [CrossRef]
29. Schwede A,, Jones N,, Engstler M,, Carrington M . 2011. The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes. Mol Biochem Parasitol 175 : 201 204.[PubMed] [CrossRef]
30. Engstler M,, Pfohl T,, Herminghaus S,, Boshart M,, Wiegertjes G,, Heddergott N,, Overath P . 2007. Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131 : 505 515.[PubMed] [CrossRef]
31. Seyfang A,, Mecke D,, Duszenko M . 1990. Degradation, recycling, and shedding of Trypanosoma brucei variant surface glycoprotein. J Protozool 37 : 546 552.[PubMed] [CrossRef]
32. Higgins MK,, Tkachenko O,, Brown A,, Reed J,, Raper J,, Carrington M . 2013. Structure of the trypanosome haptoglobin-hemoglobin receptor and implications for nutrient uptake and innate immunity. Proc Natl Acad Sci USA 110 : 1905 1910.[PubMed] [CrossRef]
33. Greif G,, Ponce de LM,, Lamolle G,, Rodriguez M,, Pineyro D,, Tavares-Marques LM,, Reyna-Bello A,, Robello C,, Alvarez-Valin F . 2013. Transcriptome analysis of the bloodstream stage from the parasite Trypanosoma vivax . BMC Genomics 14 : 149. [PubMed] [CrossRef]
34. La GF,, Magez S . 2011. Vaccination against trypanosomiasis: can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist? Hum Vaccin 7 : 1225 1233.[PubMed] [CrossRef]
35. Guirnalda P,, Murphy NB,, Nolan D,, Black SJ . 2007. Anti- Trypanosoma brucei activity in Cape buffalo serum during the cryptic phase of parasitemia is mediated by antibodies. Int J Parasitol 37 : 1391 1399.[PubMed] [CrossRef]
36. Blum ML,, Down JA,, Gurnett AM,, Carrington M,, Turner MJ,, Wiley DC . 1993. A structural motif in the variant surface glycoproteins of Trypanosoma brucei . Nature 362 : 603 609.[PubMed] [CrossRef]
37. Marcello L,, Barry JD . 2007. Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure. Genome Res 17 : 1344 1352.[PubMed] [CrossRef]
38. Metcalf P,, Blum M,, Freymann D,, Turner M,, Wiley DC . 1987. Two variant surface glycoproteins of Trypanosoma brucei of different sequence classes have similar 6 A resolution X-ray structures. Nature 325 : 84 86.[PubMed] [CrossRef]
39. Daniels JP,, Gull K,, Wickstead B . 2010. Cell biology of the trypanosome genome. Microbiol Mol Biol Rev 74 : 552 569.[PubMed] [CrossRef]
40. Siegel TN,, Gunasekera K,, Cross GA,, Ochsenreiter T . 2011. Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing. Trends Parasitol 27 : 434 441.[PubMed] [CrossRef]
41. Gunzl A,, Bruderer T,, Laufer G,, Schimanski B,, Tu LC,, Chung HM,, Lee PT,, Lee MG . 2003. RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei . Eukaryot Cell 2 : 542 551.[PubMed] [CrossRef]
42. Zomerdijk JC,, Ouellette M,, Ten Asbroek AL,, Kieft R,, Bommer AM,, Clayton CE,, Borst P . 1990. The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei . EMBO J 9 : 2791 2801.[PubMed]
43. Brandenburg J,, Schimanski B,, Nogoceke E,, Nguyen TN,, Padovan JC,, Chait BT,, Cross GA,, Gunzl A . 2007. Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex. EMBO J 26 : 4856 4866.[PubMed] [CrossRef]
44. Chaves I,, Zomerdijk J,, Dirks-Mulder A,, Dirks RW,, Raap AK,, Borst P . 1998. Subnuclear localization of the active variant surface glycoprotein gene expression site in Trypanosoma brucei . Proc Natl Acad Sci U S A 95 : 12328 12333.[PubMed] [CrossRef]
45. Navarro M,, Gull K . 2001. A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei . Nature 414 : 759 763.[PubMed] [CrossRef]
46. Berriman M,, Ghedin E,, Hertz-Fowler C,, Blandin G,, Renauld H,, Bartholomeu DC,, Lennard NJ,, Caler E,, Hamlin NE,, Haas B,, Böhme U,, Hannick L,, Aslett MA,, Shallom J,, Marcello L,, Hou L,, Wickstead B,, Alsmark UC,, Arrowsmith C,, Atkin RJ,, Barron AJ,, Bringaud F,, Brooks K,, Carrington M,, Cherevach I,, Chillingworth TJ,, Churcher C,, Clark LN,, Corton CH,, Cronin A,, Davies RM,, Doggett J,, Djikeng A,, Feldblyum T,, Field MC,, Fraser A,, Goodhead I,, Hance Z,, Harper D,, Harris BR,, Hauser H,, Hostetler J,, Ivens A,, Jagels K,, Johnson D,, Johnson J,, Jones K,, Kerhornou AX,, Koo H,, Larke N,, Landfear S,, Larkin C,, Leech V,, Line A,, Lord A,, Macleod A,, Mooney PJ,, Moule S,, Martin DM,, Morgan GW,, Mungall K,, Norbertczak H,, Ormond D,, Pai G,, Peacock CS,, Peterson J,, Quail MA,, Rabbinowitsch E,, Rajandream MA,, Reitter C,, Salzberg SL,, Sanders M,, Schobel S,, Sharp S,, Simmonds M,, Simpson AJ,, Tallon L,, Turner CM,, Tait A,, Tivey AR,, Van Aken S,, Walker D,, Wanless D,, Wang S,, White B,, White O,, Whitehead S,, Woodward J,, Wortman J,, Adams MD,, Embley TM,, Gull K,, Ullu E,, Barry JD,, Fairlamb AH,, Opperdoes F,, Barrell BG,, Donelson JE,, Hall N,, Fraser CM,, Melville SE,, El-Sayed NM . 2005. The genome of the African trypanosome Trypanosoma brucei . Science 309 : 416 422.[PubMed] [CrossRef]
47. Jackson AP,, Sanders M,, Berry A,, McQuillan J,, Aslett MA,, Quail MA,, Chukualim B,, Capewell P,, MacLeod A,, Melville SE,, Gibson W,, Barry JD,, Berriman M,, Hertz-Fowler C . 2010. The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic human african trypanosomiasis. PLoS Negl Trop Dis, 4 : e658. [PubMed] [CrossRef]
48. Hertz-Fowler C,, Figueiredo LM,, Quail MA,, Becker M,, Jackson A,, Bason N,, Brooks K,, Churcher C,, Fahkro S,, Goodhead I,, Heath P,, Kartvelishvili M,, Mungall K,, Harris D,, Hauser H,, Sanders M,, Saunders D,, Seeger K,, Sharp S,, Taylor JE,, Walker D,, White B,, Young R,, Cross GA,, Rudenko G,, Barry JD,, Louis EJ,, Berriman M . 2008. Telomeric expression sites are highly conserved in Trypanosoma brucei . PLoS ONE 3 : e3527. [PubMed] [CrossRef]
49. Navarro M,, Cross GA . 1996. DNA rearrangements associated with multiple consecutive directed antigenic switches in Trypanosoma brucei . Mol Cell Biol 16 : 3615 3625.[PubMed]
50. Young R,, Taylor JE,, Kurioka A,, Becker M,, Louis EJ,, Rudenko G . 2008. Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum . BMC Genomics 9 : 385. [PubMed] [CrossRef]
51. Barry JD,, Ginger ML,, Burton P,, McCulloch R . 2003. Why are parasite contingency genes often associated with telomeres? Int J Parasitol 33 : 29 45.[PubMed] [CrossRef]
52. Linardopoulou EV,, Williams EM,, Fan Y,, Friedman C,, Young JM,, Trask BJ . 2005. Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature 437 : 94 100.[PubMed] [CrossRef]
53. Fan C,, Zhang Y,, Yu Y,, Rounsley S,, Long M,, Wing RA . 2008. The subtelomere of Oryza sativa chromosome 3 short arm as a hot bed of new gene origination in rice. Mol Plant 1 : 839 850.[PubMed] [CrossRef]
54. Brown CA,, Murray AW,, Verstrepen KJ . 2010. Rapid expansion and functional divergence of subtelomeric gene families in yeasts. Curr Biol 20 : 895 903.[PubMed] [CrossRef]
55. Moraes Barros RR,, Marini MM,, Antonio CR,, Cortez DR,, Miyake AM,, Lima FM,, Ruiz JC,, Bartholomeu DC,, Chiurillo MA,, Ramirez JL,, da Silveira JF . 2012. Anatomy and evolution of telomeric and subtelomeric regions in the human protozoan parasite Trypanosoma cruzi . BMC Genomics 13 : 229. [PubMed] [CrossRef]
56. Shah JS,, Young JR,, Kimmel BE,, Iams KP,, Williams RO . 1987. The 5′ flanking sequence of a Trypanosoma brucei variable surface glycoprotein gene. Mol Biochem Parasitol 24 : 163 174.[PubMed] [CrossRef]
57. Ohshima K,, Kang S,, Larson JE,, Wells RD . 1996. TTA.TAA triplet repeats in plasmids form a non-H bonded structure. J Biol Chem 271 : 16784 16791.[PubMed] [CrossRef]
58. Pan X,, Liao Y,, Liu Y,, Chang P,, Liao L,, Yang L,, Li H . 2010. Transcription of AAT*ATT triplet repeats in Escherichia coli is silenced by H-NS and IS1E transposition. PLoS One 5 : e14271. [PubMed] [CrossRef]
59. Borst P,, Rudenko G,, Blundell PA,, van Leeuwen F,, Cross MA,, McCulloch R,, Gerrits H,, Chaves IM . 1997. Mechanisms of antigenic variation in African trypanosomes. Behring Inst Mitt 1 15.[PubMed]
60. Pays E,, Lips S,, Nolan D,, Vanhamme L,, Perez-Morga D . 2001. The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts. Mol Biochem Parasitol 114 : 1 16.[PubMed] [CrossRef]
61. McCulloch R,, Horn D . 2009. What has DNA sequencing revealed about the VSG expression sites of African trypanosomes? Trends Parasitol 25 : 359 63.[PubMed] [CrossRef]
62. Siegel TN,, Hekstra DR,, Wang X,, Dewell S,, Cross GA . 2010. Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Res 38 : 4946 4957.[PubMed] [CrossRef]
63. Bitter W,, Gerrits H,, Kieft R,, Borst P . 1998. The role of transferrin-receptor variation in the host range of Trypanosoma brucei . Nature 391 : 499 502.[PubMed] [CrossRef]
64. van Luenen HG,, Kieft R,, Mussmann R,, Engstler M,, ter Riet B,, Borst P . 2005. Trypanosomes change their transferrin receptor expression to allow effective uptake of host transferrin. Mol Microbiol 58 : 151 165.[PubMed] [CrossRef]
65. Gerrits H,, Mussmann R,, Bitter W,, Kieft R,, Borst P . 2002. The physiological significance of transferrin receptor variations in Trypanosoma brucei . Mol Biochem Parasitol 119 : 237 247.[PubMed] [CrossRef]
66. Steverding D . 2006. On the significance of host antibody response to the Trypanosoma brucei transferrin receptor during chronic infection. Microbes Infect 8 : 2777 2782.[PubMed] [CrossRef]
67. Salmon D,, Paturiaux-Hanocq F,, Poelvoorde P,, Vanhamme L,, Pays E . 2005. Trypanosoma brucei: growth differences in different mammalian sera are not due to the species-specificity of transferrin. Exp Parasitol 109 : 188 194.[PubMed] [CrossRef]
68. Cordon-Obras C,, Cano J,, Gonzalez-Pacanowska D,, Benito A,, Navarro M,, Bart JM . 2013. Trypanosoma brucei gambiense Adaptation to Different Mammalian Sera Is Associated with VSG Expression Site Plasticity. PLoS ONE 8 : e85072. [PubMed] [CrossRef]
69. Salmon D,, Vanwalleghem G,, Morias Y,, Denoeud J,, Krumbholz C,, Lhommé F,, Bachmaier S,, Kador M,, Gossmann J,, Dias FB,, De Muylder G,, Uzureau P,, Magez S,, Moser M,, De Baetselier P,, Van Den Abbeele J,, Beschin A,, Boshart M,, Pays E . 2012. Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science 337 : 463 466.[PubMed] [CrossRef]
70. Xong HV,, Vanhamme L,, Chamekh M,, Chimfwembe CE,, Van den AJ,, Pays A,, Van Meirvenne N,, Hamers R,, De Baetselier P,, Pays E . 1998. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense . Cell 95 : 839 846.[PubMed] [CrossRef]
71. Wickstead B,, Ersfeld K,, Gull K . 2004. The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes. Genome Res 14 : 1014 1024.[PubMed] [CrossRef]
72. Ginger ML,, Blundell PA,, Lewis AM,, Browitt A,, Gunzl A,, Barry JD . 2002. Ex Vivo and In Vitro Identification of a Consensus Promoter for VSG Genes Expressed by Metacyclic-Stage Trypanosomes in the Tsetse Fly. Eukaryot Cell 1 : 1000 1009.[PubMed] [CrossRef]
73. Sharma R,, Gluenz E,, Peacock L,, Gibson W,, Gull K,, Carrington M . 2009. The heart of darkness: growth and form of Trypanosoma brucei in the tsetse fly. Trends Parasitol 25 : 517 524.[PubMed] [CrossRef]
74. Kolev NG,, Ramey-Butler K,, Cross GA,, Ullu E,, Tschudi C . 2012. Developmental progression to infectivity in Trypanosoma brucei triggered by an RNA-binding protein. Science 338 : 1352 1353.[PubMed] [CrossRef]
75. Jackson AP,, Allison HC,, Barry JD,, Field MC,, Hertz-Fowler C,, Berriman M . 2013. A cell-surface phylome for African trypanosomes. PLoS Negl Trop Dis 7 : e2121. [PubMed] [CrossRef]
76. Marcello L,, Menon S,, Ward P,, Wilkes JM,, Jones NG,, Carrington M,, Barry JD . 2007. VSGdb: a database for trypanosome variant surface glycoproteins, a large and diverse family of coiled coil proteins. BMC Bioinformatics 8 : 143. [PubMed] [CrossRef]
77. Weiden M,, Osheim YN,, Beyer AL,, Van der Ploeg LH . 1991. Chromosome structure: DNA nucleotide sequence elements of a subset of the minichromosomes of the protozoan Trypanosoma brucei . Mol Cell Biol 11 : 3823 3834.[PubMed]
78. Akiyoshi B,, Gull K . 2014. Discovery of Unconventional Kinetochores in Kinetoplastids. Cell 156 : 1247 1258.[PubMed] [CrossRef]
79. Rothwell V,, Aline R Jr,, Parsons M,, Agabian N,, Stuart K . 1985. Expression of a minichromosomal variant surface glycoprotein gene in Trypanosoma brucei . Nature 313 : 595 597.[PubMed] [CrossRef]
80. Melville SE,, Gerrard CS,, Blackwell JM . 1999. Multiple causes of size variation in the diploid megabase chromosomes of African trypanosomes. Chromosome Res 7 : 191 203.[PubMed] [CrossRef]
81. Callejas S,, Leech V,, Reitter C,, Melville S . 2006. Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length. Genome Res 16 : 1109 1118.[PubMed] [CrossRef]
82. MacLean RC,, Torres-Barcelo C,, Moxon R . 2013. Evaluating evolutionary models of stress-induced mutagenesis in bacteria. Nat Rev Genet 14 : 221 227.[PubMed] [CrossRef]
83. Gjini E,, Haydon DT,, Barry JD,, Cobbold CA . 2012. The Impact of Mutation and Gene Conversion on the Local Diversification of Antigen Genes in African Trypanosomes. Mol Biol Evol 29 : 3321 3331.[PubMed] [CrossRef]
84. Jackson AP,, Berry A,, Aslett M,, Allison HC,, Burton P,, Vavrova-Anderson J,, Brown R,, Browne H,, Corton N,, Hauser H,, Gamble J,, Gilderthorp R,, Marcello L,, McQuillan J,, Otto TD,, Quail MA,, Sanders MJ,, van Tonder A,, Ginger ML,, Field MC,, Barry JD,, Hertz-Fowler C,, Berriman M . 2012. Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. Proc Natl Acad Sci USA 109 : 3416 3421.[PubMed] [CrossRef]
85. Borst P,, Ulbert S . 2001. Control of VSG gene expression sites. Mol Biochem Parasitol 114 : 17 27.[PubMed] [CrossRef]
86. Borst P . 2002. Antigenic variation and allelic exclusion. Cell 109 : 5 8.[PubMed] [CrossRef]
87. Pays E . 2005. Regulation of antigen gene expression in Trypanosoma brucei . Trends Parasitol 21 : 517 520.[PubMed] [CrossRef]
88. Navarro M,, Penate X,, Landeira D . 2007. Nuclear architecture underlying gene expression in Trypanosoma brucei . Trends Microbiol 15 : 263 270.[PubMed] [CrossRef]
89. Schwede A,, Carrington M . 2010. Bloodstream form Trypanosome plasma membrane proteins: antigenic variation and invariant antigens. Parasitology 137 : 2029 2039.[PubMed] [CrossRef]
90. Chaves I,, Rudenko G,, Dirks-Mulder A,, Cross M,, Borst P . 1999. Control of variant surface glycoprotein gene-expression sites in Trypanosoma brucei . EMBO J 18 : 4846 4855.[PubMed] [CrossRef]
91. Ulbert S,, Chaves I,, Borst P . 2002. Expression site activation in Trypanosoma brucei with three marked variant surface glycoprotein gene expression sites. Mol Biochem Parasitol 120 : 225 235.[PubMed] [CrossRef]
92. Baltz T,, Giroud C,, Baltz D,, Roth C,, Raibaud A,, Eisen H . 1986. Stable expression of two variable surface glycoproteins by cloned Trypanosoma equiperdum . Nature 319 : 602 604.[PubMed] [CrossRef]
93. Munoz-Jordan JL,, Davies KP,, Cross GA . 1996. Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei . Science 272 : 1795 1797.[PubMed] [CrossRef]
94. Yang X,, Figueiredo LM,, Espinal A,, Okubo E,, Li B . 2009. RAP1 is essential for silencing telomeric variant surface glycoprotein genes in Trypanosoma brucei . Cell 137 : 99 109.[PubMed] [CrossRef]
95. Denninger V,, Fullbrook A,, Bessat M,, Ersfeld K,, Rudenko G . 2010. The FACT subunit TbSpt16 is involved in cell cycle specific control of VSG expression sites in Trypanosoma brucei . Mol Microbiol 78 : 459 474.[PubMed] [CrossRef]
96. Povelones ML,, Gluenz E,, Dembek M,, Gull K,, Rudenko G . 2012. Histone H1 Plays a Role in Heterochromatin Formation and VSG Expression Site Silencing in Trypanosoma brucei . PLoS Pathog 8 : e1003010. [PubMed] [CrossRef]
97. Alsford S,, Horn D . 2012. Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei . Nucleic Acids Res 40 : 10150 10160.[PubMed] [CrossRef]
98. Narayanan MS,, Rudenko G . 2013. TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes. Nucleic Acids Res 41 : 2981 2992.[PubMed] [CrossRef]
99. DuBois KN,, Alsford S,, Holden JM,, Buisson J,, Swiderski M,, Bart JM,, Ratushny AV,, Wan Y,, Bastin P,, Barry JD,, Navarro M,, Horn D,, Aitchison JD,, Rout MP,, Field MC . 2012. NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biol 10 : e1001287. [PubMed] [CrossRef]
100. Vanhamme L,, Poelvoorde P,, Pays A,, Tebabi P,, Van Xong H,, Pays E . 2000. Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei . Mol Microbiol 36 : 328 340.[PubMed] [CrossRef]
101. Nguyen TN,, Muller LS,, Park SH,, Siegel TN,, Gunzl A . 2013. Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei. Nucleic Acids Res 42 : 3164 3176.[PubMed] [CrossRef]
102. Figueiredo LM,, Janzen CJ,, Cross GA . 2008. A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biol 6 : e161. [PubMed] [CrossRef]
103. Stockdale C,, Swiderski MR,, Barry JD,, McCulloch R . 2008. Antigenic variation in Trypanosoma brucei: joining the DOTs. PLoS Biol 6 : e185. [PubMed] [CrossRef]
104. Landeira D,, Bart JM,, Van Tyne D,, Navarro M . 2009. Cohesin regulates VSG monoallelic expression in trypanosomes. J Cell Biol 186 : 243 254.[PubMed] [CrossRef]
105. Tiengwe C,, Marcello L,, Farr H,, Dickens N,, Kelly S,, Swiderski M,, Vaughan D,, Gull K,, Barry JD,, Bell SD,, McCulloch R . 2012. Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei . Cell Rep 2 : 185 197.[PubMed] [CrossRef]
106. Benmerzouga I,, Concepcion-Acevedo J,, Kim HS,, Vandoros AV,, Cross GA,, Klingbeil MM,, Li B . 2013. Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching. Mol Microbiol 87 : 196 210.[PubMed] [CrossRef]
107. Kim HS,, Park SH,, Gunzl A,, Cross GA . 2013. MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei. PLoS ONE 8 : e57001. [PubMed] [CrossRef]
108. Dobson R,, Stockdale C,, Lapsley C,, Wilkes J,, McCulloch R . 2011. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation. Mol Microbiol 81 : 434 456.[PubMed] [CrossRef]
109. Hartley CL,, McCulloch R . 2008. Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination. Mol Microbiol 68 : 1237 1251.[PubMed] [CrossRef]
110. McCulloch R,, Barry JD . 1999. A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation. Genes Dev 13 : 2875 2888.[PubMed] [CrossRef]
111. Sheader K,, te VD,, Rudenko G . 2004. Bloodstream form-specific up-regulation of silent vsg expression sites and procyclin in Trypanosoma brucei after inhibition of DNA synthesis or DNA damage. J Biol Chem 279 : 13363 13374.[PubMed] [CrossRef]
112. Liu AY,, Van der Ploeg LH,, Rijsewijk FA,, Borst P . 1983. The transposition unit of variant surface glycoprotein gene 118 of Trypanosoma brucei. Presence of repeated elements at its border and absence of promoter-associated sequences. J Mol Biol 167 : 57 75.[PubMed] [CrossRef]
113. Pays E,, Van Assel S,, Laurent M,, Dero B,, Michiels F,, Kronenberger P,, Matthyssens G,, Van Meirvenne N,, Le Ray D,, Steinert M . 1983. At least two transposed sequences are associated in the expression site of a surface antigen gene in different trypanosome clones. Cell 34 : 359 369.[PubMed] [CrossRef]
114. McCulloch R,, Rudenko G,, Borst P . 1997. Gene conversions mediating antigenic variation in Trypanosoma brucei can occur in variant surface glycoprotein expression sites lacking 70- base-pair repeat sequences. Mol Cell Biol 17 : 833 843.[PubMed]
115. Bernards A,, Van der Ploeg LH,, Frasch AC,, Borst P,, Boothroyd JC,, Coleman S,, Cross GA . 1981. Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3′ end. Cell 27 : 497 505.[PubMed] [CrossRef]
116. de Lange T,, Kooter JM,, Michels PA,, Borst P . 1983. Telomere conversion in trypanosomes. Nucleic Acids Res 11 : 8149 8165.[PubMed] [CrossRef]
117. Kim HS,, Cross GA . 2010. TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei . PLoS Pathog 6 : e1000992. [PubMed] [CrossRef]
118. Pays E,, Guyaux M,, Aerts D,, Van Meirvenne N,, Steinert M . 1985. Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes. Nature 316 : 562 564.[PubMed] [CrossRef]
119. Rudenko G,, McCulloch R,, Dirks-Mulder A,, Borst P . 1996. Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei . Mol Biochem Parasitol 80 : 65 75.[PubMed] [CrossRef]
120. Thon G,, Baltz T,, Giroud C,, Eisen H . 1990. Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes Dev 4 : 1374 1383.[PubMed] [CrossRef]
121. Roth C,, Bringaud F,, Layden RE,, Baltz T,, Eisen H . 1989. Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. Proc Natl Acad Sci USA 86 : 9375 9379.[PubMed] [CrossRef]
122. Thon G,, Baltz T,, Eisen H . 1989. Antigenic diversity by the recombination of pseudogenes. Genes Dev 3 : 1247 1254.[PubMed] [CrossRef]
123. Roth C,, Jacquemot C,, Giroud C,, Bringaud F,, Eisen H,, Baltz T . 1991. Antigenic variation in Trypanosoma equiperdum . Res Microbiol 142 : 725 730.[PubMed] [CrossRef]
124. Hall JP,, Wang H,, Barry JD . 2013. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathog 9 : e1003502. [PubMed] [CrossRef]
125. Barbet AF,, Kamper SM . 1993. The importance of mosaic genes to trypanosome survival. Parasitol Today 9 : 63 66.[PubMed] [CrossRef]
126. Kamper SM,, Barbet AF . 1992. Surface epitope variation via mosaic gene formation is potential key to long-term survival of Trypanosoma brucei . Mol Biochem Parasitol 53 : 33 44.[PubMed] [CrossRef]
127. Boothroyd CE,, Dreesen O,, Leonova T,, Ly KI,, Figueiredo LM,, Cross GA,, Papavasiliou FN . 2009. A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei . Nature 459 : 278 281.[PubMed] [CrossRef]
128. Glover L,, Alsford S,, Horn D . 2013. DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in african trypanosomes. PLoS Pathog 9 : e1003260. [PubMed] [CrossRef]
129. Aitcheson N,, Talbot S,, Shapiro J,, Hughes K,, Adkin C,, Butt T,, Sheader K,, Rudenko G . 2005. VSG switching in Trypanosoma brucei: antigenic variation analysed using RNAi in the absence of immune selection. Mol Microbiol 57 : 1608 1622.[PubMed] [CrossRef]
130. Cahoon LA,, Seifert HS . 2011. Focusing homologous recombination: pilin antigenic variation in the pathogenic Neisseria . Mol Microbiol 81 : 1136 1143.[PubMed] [CrossRef]
131. Vink C,, Rudenko G,, Seifert HS . 2011. Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev 36 : 917 948.[PubMed] [CrossRef]
132. San Filippo J,, Sung P,, Klein H . 2008. Mechanism of Eukaryotic Homologous Recombination. Annu Rev Biochem 77 : 229 257.[PubMed] [CrossRef]
133. Koomey M,, Gotschlich EC,, Robbins K,, Bergstrom S,, Swanson J . 1987. Effects of recA mutations on pilus antigenic variation and phase transitions in Neisseria gonorrhoeae . Genetics 117 : 391 398.[PubMed]
134. Mehr IJ,, Seifert HS . 1998. Differential roles of homologous recombination pathways in Neisseria gonorrhoeae pilin antigenic variation, DNA transformation and DNA repair. Mol Microbiol 30 : 697 710.[PubMed] [CrossRef]
135. Helm RA,, Seifert HS . 2009. Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria gonorrhoeae . J Bacteriol 191 : 5613 5621.[PubMed] [CrossRef]
136. Roy R,, Chun J,, Powell SN . 2012. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 12 : 68 78.[PubMed] [CrossRef]
137. Trenaman A,, Hartley C,, Prorocic M,, Passos-Silva DG,, van den Hoek M,, Nechyporuk-Zloy V,, Machado CR,, McCulloch R . 2013. Trypanosoma brucei BRCA2 acts in a life cycle-specific genome stability process and dictates BRC repeat number-dependent RAD51 subnuclear dynamics. Nucleic Acids Res 41 : 943 960.[PubMed] [CrossRef]
138. Stohl EA,, Seifert HS . 2001. The recX gene potentiates homologous recombination in Neisseria gonorrhoeae . Mol Microbiol 40 : 1301 1310.[PubMed] [CrossRef]
139. Gruenig MC,, Stohl EA,, Chitteni-Pattu S,, Seifert HS,, Cox MM . 2010. Less is more: Neisseria gonorrhoeae RecX protein stimulates recombination by inhibiting RecA. J Biol Chem 285 : 37188 37197.[PubMed] [CrossRef]
140. Cardenas PP,, Carrasco B,, Defeu SC,, Cesar CE,, Herr K,, Kaufenstein M,, Graumann PL,, Alonso JC . 2012. RecX facilitates homologous recombination by modulating RecA activities. PLoS Genet 8 : e1003126. [PubMed] [CrossRef]
141. Suwaki N,, Klare K,, Tarsounas M . 2011. RAD51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol 22 : 898 905.[PubMed] [CrossRef]
142. Jensen RB,, Ozes A,, Kim T,, Estep A,, Kowalczykowski SC . 2013. BRCA2 is epistatic to the RAD51 paralogs in response to DNA damage. DNA Repair (Amst) 12 : 306 311.[PubMed] [CrossRef]
143. Chun J,, Buechelmaier ES,, Powell SN . 2013. Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway. Mol Cell Biol 33 : 387 395.[PubMed] [CrossRef]
144. Proudfoot C,, McCulloch R . 2005. Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation. Nucleic Acids Res 33 : 6906 6919.[PubMed] [CrossRef]
145. Kim HS,, Cross GA . 2011. Identification of Trypanosoma brucei RMI1/BLAP75 Homologue and Its Roles in Antigenic Variation. PLoS One 6 : e25313. [PubMed] [CrossRef]
146. Killoran MP,, Kohler PL,, Dillard JP,, Keck JL . 2009. RecQ DNA helicase HRDC domains are critical determinants in Neisseria gonorrhoeae pilin antigenic variation and DNA repair. Mol Microbiol 71 : 158 171.[PubMed] [CrossRef]
147. Cahoon LA,, Manthei KA,, Rotman E,, Keck JL,, Seifert HS . 2013. Neisseria gonorrhoeae RecQ helicase HRDC domains are essential for efficient binding and unwinding of the pilE guanine quartet structure required for pilin antigenic variation. J Bacteriol 195 : 2255 2261.[PubMed] [CrossRef]
148. Cahoon LA,, Seifert HS . 2009. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae . Science 325 : 764 767.[PubMed] [CrossRef]
149. Cahoon LA,, Seifert HS . 2013. Transcription of a cis-acting, noncoding, small RNA is required for pilin antigenic variation in Neisseria gonorrhoeae . PLoS Pathog 9 : e1003074. [PubMed] [CrossRef]
150. Kuryavyi V,, Cahoon LA,, Seifert HS,, Patel DJ . 2012. RecA-binding pilE G4 sequence essential for pilin antigenic variation forms monomeric and 5′ end-stacked dimeric parallel G-quadruplexes. Structure 20 : 2090 2102.[PubMed] [CrossRef]
151. Stracker TH,, Petrini JH . 2011. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 12 : 90 103.[PubMed] [CrossRef]
152. Robinson NP,, McCulloch R,, Conway C,, Browitt A,, Barry JD . 2002. Inactivation of Mre11 Does Not Affect VSG Gene Duplication Mediated by Homologous Recombination in Trypanosoma brucei . J Biol Chem 277 : 26185 26193.[PubMed] [CrossRef]
153. Tan KS,, Leal ST,, Cross GA . 2002. Trypanosoma brucei MRE11 is non-essential but influences growth, homologous recombination and DNA double-strand break repair. Mol Biochem Parasitol 125 : 11 21.[PubMed] [CrossRef]
154. Jiricny J . 2013. Postreplicative mismatch repair. Cold Spring Harb Perspect Biol 5 : a012633. [PubMed] [CrossRef]
155. Bell JS,, McCulloch R . 2003. Mismatch repair regulates homologous recombination, but has little influence on antigenic variation, in Trypanosoma brucei . J Biol Chem 278 : 45182 45188.[PubMed] [CrossRef]
156. Bell JS,, Harvey TI,, Sims AM,, McCulloch R . 2004. Characterization of components of the mismatch repair machinery in Trypanosoma brucei . Mol Microbiol 51 : 159 173.[PubMed] [CrossRef]
157. Barnes RL,, McCulloch R . 2007. Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases. Nucleic Acids Res 35 : 3478 3493.[PubMed] [CrossRef]
158. Slean MM,, Panigrahi GB,, Ranum LP,, Pearson CE . 2008. Mutagenic roles of DNA “repair” proteins in antibody diversity and disease-associated trinucleotide repeat instability. DNA Repair (Amst) 7 : 1135 1154.[PubMed] [CrossRef]
159. Hill SA,, Davies JK . 2009. Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms. FEMS Microbiol Rev 33 : 521 530.[PubMed] [CrossRef]
160. Criss AK,, Bonney KM,, Chang RA,, Duffin PM,, LeCuyer BE,, Seifert HS . 2010. Mismatch correction modulates mutation frequency and pilus phase and antigenic variation in Neisseria gonorrhoeae . J Bacteriol 192 : 316 325.[PubMed] [CrossRef]
161. Ottaviani D,, Lecain M,, Sheer D . 2014. The role of microhomology in genomic structural variation. Trends Genet 30 : 85 94.[PubMed] [CrossRef]
162. Conway C,, McCulloch R,, Ginger ML,, Robinson NP,, Browitt A,, Barry JD . 2002. Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes. J Biol Chem 277 : 21269 21277.[PubMed] [CrossRef]
163. Janzen CJ,, Lander F,, Dreesen O,, Cross GA . 2004. Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei . Nucleic Acids Res 32 : 6575 6584.[PubMed] [CrossRef]
164. Gill EE,, Fast NM . 2007. Stripped-down DNA repair in a highly reduced parasite. BMC Mol Biol 8 : 24. [PubMed] [CrossRef]
165. Burton P,, McBride DJ,, Wilkes JM,, Barry JD,, McCulloch R . 2007. Ku Heterodimer-Independent End Joining in Trypanosoma brucei Cell Extracts Relies upon Sequence Microhomology. Eukaryot Cell 6 : 1773 1781.[PubMed] [CrossRef]
166. Conway C,, Proudfoot C,, Burton P,, Barry JD,, McCulloch R . 2002. Two pathways of homologous recombination in Trypanosoma brucei . Mol Microbiol 45 : 1687 1700.[PubMed] [CrossRef]
167. Glover L,, McCulloch R,, Horn D . 2008. Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes. Nucleic Acids Res 36 : 2608 2618.[PubMed] [CrossRef]
168. Glover L,, Jun J,, Horn D . 2011. Microhomology-mediated deletion and gene conversion in African trypanosomes. Nucleic Acids Res 39 : 1372 1380.[PubMed] [CrossRef]
169. Liveris D,, Mulay V,, Sandigursky S,, Schwartz I . 2008. Borrelia burgdorferi vlsE antigenic variation is not mediated by RecA. Infect Immun 76 : 4009 4018.[PubMed] [CrossRef]
170. Dresser AR,, Hardy PO,, Chaconas G . 2009. Investigation of the genes involved in antigenic switching at the vlsE locus in Borrelia burgdorferi: an essential role for the RuvAB branch migrase. PLoS Pathog 5 : e1000680. [PubMed] [CrossRef]
171. Lin T,, Gao L,, Edmondson DG,, Jacobs MB,, Philipp MT,, Norris SJ . 2009. Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi . PLoS Pathog 5 : e1000679. [PubMed] [CrossRef]
172. Mir T,, Huang SH,, Kobryn K . 2013. The telomere resolvase of the Lyme disease spirochete, Borrelia burgdorferi, promotes DNA single-strand annealing and strand exchange. Nucleic Acids Res 41 : 10438 10448.[PubMed] [CrossRef]
173. Barry JD . 1997. The relative significance of mechanisms of antigenic variation in African trypanosomes. Parasitol Today 13 : 212 218.[PubMed] [CrossRef]
174. Barry D,, McCulloch R . 2009. Molecular microbiology: a key event in survival. Nature 459 : 172 173.[PubMed] [CrossRef]
175. Keim C,, Kazadi D,, Rothschild G,, Basu U . 2013. Regulation of AID, the B-cell genome mutator. Genes Dev 27 : 1 17.[PubMed] [CrossRef]
176. Durkin SG,, Glover TW . 2007. Chromosome fragile sites. Annu Rev Genet 41 : 169 192.[PubMed] [CrossRef]
177. Ozeri-Galai E,, Lebofsky R,, Rahat A,, Bester AC,, Bensimon A,, Kerem B . 2011. Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell 43 : 122 131.[PubMed] [CrossRef]
178. Klar AJ . 2007. Lessons learned from studies of fission yeast mating-type switching and silencing. Annu Rev Genet 41 : 213 236.[PubMed] [CrossRef]
179. Yakisich JS,, Kapler GM . 2006. Deletion of the Tetrahymena thermophila rDNA replication fork barrier region disrupts macronuclear rDNA excision and creates a fragile site in the micronuclear genome. Nucleic Acids Res 34 : 620 634.[PubMed] [CrossRef]
180. Dreesen O,, Li B,, Cross GA . 2007. Telomere structure and function in trypanosomes: a proposal. Nat Rev Microbiol 5 : 70 75.[PubMed] [CrossRef]
181. Hovel-Miner GA,, Boothroyd CE,, Mugnier M,, Dreesen O,, Cross GA,, Papavasiliou FN . 2012. Telomere Length Affects the Frequency and Mechanism of Antigenic Variation in Trypanosoma brucei . PLoS Pathog 8 : e1002900. [PubMed] [CrossRef]
182. Dreesen O,, Li B,, Cross GA . 2005. Telomere structure and shortening in telomerase-deficient Trypanosoma brucei . Nucleic Acids Res 33 : 4536 4543.[PubMed] [CrossRef]
183. Dreesen O,, Cross GA . 2006. Telomerase-independent stabilization of short telomeres in Trypanosoma brucei . Mol Cell Biol 26 : 4911 4919.[PubMed] [CrossRef]
184. Meeus PF,, Brayton KA,, Palmer GH,, Barbet AF . 2003. Conservation of a gene conversion mechanism in two distantly related paralogues of Anaplasma marginale . Mol Microbiol 47 : 633 643.[PubMed] [CrossRef]
185. Giacani L,, Molini BJ,, Kim EY,, Godornes BC,, Leader BT,, Tantalo LC,, Centurion-Lara A,, Lukehart SA . 2010. Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis. J Immunol 184 : 3822 3829.[PubMed] [CrossRef]
186. Iverson-Cabral SL,, Astete SG,, Cohen CR,, Totten PA . 2007. mgpB and mgpC sequence diversity in Mycoplasma genitalium is generated by segmental reciprocal recombination with repetitive chromosomal sequences. Mol Microbiol 66 : 55 73. [PubMed] [CrossRef]
187. Ma L,, Jensen JS,, Myers L,, Burnett J,, Welch M,, Jia Q,, Martin DH . 2007. Mycoplasma genitalium: an efficient strategy to generate genetic variation from a minimal genome. Mol Microbiol 66 : 220 236.[PubMed] [CrossRef]
188. Burgos R,, Wood GE,, Young L,, Glass JI,, Totten PA . 2012. RecA mediates MgpB and MgpC phase and antigenic variation in Mycoplasma genitalium, but plays a minor role in DNA repair. Mol Microbiol 85 : 669 683.[PubMed] [CrossRef]
189. Barbet AF,, Myler PJ,, Williams RO,, McGuire TC . 1989. Shared surface epitopes among trypanosomes of the same serodeme expressing different variable surface glycoprotein genes. Mol Biochem Parasitol 32 : 191 199.[PubMed] [CrossRef]
190. Sheader K,, Vaughan S,, Minchin J,, Hughes K,, Gull K,, Rudenko G . 2005. Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes. Proc Natl Acad Sci USA 102 : 8716 8721.[PubMed] [CrossRef]