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

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

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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

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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. doi:10.1128/microbiolspec.MDNA3-0016-2014.f1

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
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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). doi:10.1128/microbiolspec.MDNA3-0016-2014.f2

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
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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. doi:10.1128/microbiolspec.MDNA3-0016-2014.f3

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
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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. doi:10.1128/microbiolspec.MDNA3-0016-2014.f4

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
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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. doi:10.1128/microbiolspec.MDNA3-0016-2014.f5

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
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References

/content/book/10.1128/9781555819217.chap19
1. Brockhurst MA,, Koskella B . 2013. Experimental coevolution of species interactions. Trends Ecol Evol 28 : 367375.[PubMed] [CrossRef]
2. Hirano M,, Das S,, Guo P,, Cooper MD . 2011. The evolution of adaptive immunity in vertebrates. Adv Immunol 109 : 125157.[PubMed] [CrossRef]
3. Sniegowski PD,, Murphy HA . 2006. Evolvability. Curr Biol 16 : R831R834.[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 : 424439.[PubMed] [CrossRef]
7. Borst P, . 2002. Antigenic Variation in Eukaryotic Parasites, p 953971. 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 : 170.[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 : 281293.[PubMed]
10. Deitsch KW,, Lukehart SA,, Stringer JR . 2009. Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat Rev Microbiol 7 : 493503.[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 : 227231.[PubMed] [CrossRef]
12. Norris SJ . 2006. Antigenic variation with a twist—the Borrelia story. Mol Microbiol 60 : 13191322.[PubMed] [CrossRef]
13. Barrett MP,, Burchmore RJ,, Stich A,, Lazzari JO,, Frasch AC,, Cazzulo JJ,, Krishna S . 2003. The trypanosomiases. Lancet 362 : 14691480.[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 : 19992004.[PubMed] [CrossRef]
15. Barbet AF,, McGuire TC . 1978. Crossreacting determinants in variant-specific surface antigens of African trypanosomes. Proc Natl Acad Sci USA 75 : 19891993.[PubMed] [CrossRef]
16. Barry JD . 1986. Antigenic variation during Trypanosoma vivax infections of different host species. Parasitology 92 : 5165.[PubMed] [CrossRef]
17. Vickerman K . 1978. Antigenic variation in trypanosomes. Nature 273 : 613617.[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 : 11251126.[PubMed] [CrossRef]
19. Cross GA . 1975. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei . Parasitology 71 : 393417.[PubMed] [CrossRef]
20. Borst P,, Cross GA . 1982. Molecular basis for trypanosome antigenic variation. Cell 29 : 291303.[PubMed] [CrossRef]
21. Morrison LJ,, Marcello L,, McCulloch R . 2009. Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity. Cell Microbiol 11 : 17241734.[PubMed] [CrossRef]
22. Horn D . 2009. Antigenic variation: extending the reach of telomeric silencing. Curr Biol 19 : R496R498.[PubMed] [CrossRef]
23. Rudenko G . 2011. African trypanosomes: the genome and adaptations for immune evasion. Essays Biochem 51 : 4762.[PubMed]
24. Horn D,, McCulloch R . 2010. Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Curr Opin Microbiol 13 : 700705.[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 : 19841993.[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 : 354365.[PubMed] [CrossRef]
27. Barry JD,, Hall JP,, Plenderleith L . 2012. Genome hyperevolution and the success of a parasite. Ann NY Acad Sci 1267 : 1117.[PubMed] [CrossRef]
28. Barbour AG,, Restrepo BI . 2000. Antigenic variation in vector-borne pathogens. Emerg Infect Dis 6 : 449457.[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 : 201204.[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 : 505515.[PubMed] [CrossRef]
31. Seyfang A,, Mecke D,, Duszenko M . 1990. Degradation, recycling, and shedding of Trypanosoma brucei variant surface glycoprotein. J Protozool 37 : 546552.[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 : 19051910.[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 : 12251233.[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 : 13911399.[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 : 603609.[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 : 13441352.[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 : 8486.[PubMed] [CrossRef]
39. Daniels JP,, Gull K,, Wickstead B . 2010. Cell biology of the trypanosome genome. Microbiol Mol Biol Rev 74 : 552569.[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 : 434441.[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 : 542551.[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 : 27912801.[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 : 48564866.[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 : 1232812333.[PubMed] [CrossRef]
45. Navarro M,, Gull K . 2001. A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei . Nature 414 : 759763.[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 : 416422.[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 : 36153625.[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 : 2945.[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 : 94100.[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 : 839850.[PubMed] [CrossRef]
54. Brown CA,, Murray AW,, Verstrepen KJ . 2010. Rapid expansion and functional divergence of subtelomeric gene families in yeasts. Curr Biol 20 : 895903.[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 : 163174.[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 : 1678416791.[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 115.[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 : 116.[PubMed] [CrossRef]
61. McCulloch R,, Horn D . 2009. What has DNA sequencing revealed about the VSG expression sites of African trypanosomes? Trends Parasitol 25 : 35963.[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 : 49464957.[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 : 499502.[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 : 151165.[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 : 237247.[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 : 27772782.[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 : 188194.[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 : 463466.[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 : 839846.[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 : 10141024.[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 : 10001009.[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 : 517524.[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 : 13521353.[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 : 38233834.[PubMed]
78. Akiyoshi B,, Gull K . 2014. Discovery of Unconventional Kinetochores in Kinetoplastids. Cell 156 : 12471258.[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 : 595597.[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 : 191203.[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 : 11091118.[PubMed] [CrossRef]
82. MacLean RC,, Torres-Barcelo C,, Moxon R . 2013. Evaluating evolutionary models of stress-induced mutagenesis in bacteria. Nat Rev Genet 14 : 221227.[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 : 33213331.[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 : 34163421.[PubMed] [CrossRef]
85. Borst P,, Ulbert S . 2001. Control of VSG gene expression sites. Mol Biochem Parasitol 114 : 1727.[PubMed] [CrossRef]
86. Borst P . 2002. Antigenic variation and allelic exclusion. Cell 109 : 58.[PubMed] [CrossRef]
87. Pays E . 2005. Regulation of antigen gene expression in Trypanosoma brucei . Trends Parasitol 21 : 517520.[PubMed] [CrossRef]
88. Navarro M,, Penate X,, Landeira D . 2007. Nuclear architecture underlying gene expression in Trypanosoma brucei . Trends Microbiol 15 : 263270.[PubMed] [CrossRef]
89. Schwede A,, Carrington M . 2010. Bloodstream form Trypanosome plasma membrane proteins: antigenic variation and invariant antigens. Parasitology 137 : 20292039.[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 : 48464855.[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 : 225235.[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 : 602604.[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 : 17951797.[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 : 99109.[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 : 459474.[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 : 1015010160.[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 : 29812992.[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 : 328340.[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 : 31643176.[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 : 243254.[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 : 185197.[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 : 196210.[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 : 434456.[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 : 12371251.[PubMed] [CrossRef]
110. McCulloch R,, Barry JD . 1999. A role for RAD51 and homologous recombination in Trypanosoma brucei antigenic variation. Genes Dev 13 : 28752888.[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 : 1336313374.[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 : 5775.[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 : 359369.[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 : 833843.[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 : 497505.[PubMed] [CrossRef]
116. de Lange T,, Kooter JM,, Michels PA,, Borst P . 1983. Telomere conversion in trypanosomes. Nucleic Acids Res 11 : 81498165.[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 : 562564.[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 : 6575.[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 : 13741383.[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 : 93759379.[PubMed] [CrossRef]
122. Thon G,, Baltz T,, Eisen H . 1989. Antigenic diversity by the recombination of pseudogenes. Genes Dev 3 : 12471254.[PubMed] [CrossRef]
123. Roth C,, Jacquemot C,, Giroud C,, Bringaud F,, Eisen H,, Baltz T . 1991. Antigenic variation in Trypanosoma equiperdum . Res Microbiol 142 : 725730.[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 : 6366.[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 : 3344.[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 : 278281.[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 : 16081622.[PubMed] [CrossRef]
130. Cahoon LA,, Seifert HS . 2011. Focusing homologous recombination: pilin antigenic variation in the pathogenic Neisseria . Mol Microbiol 81 : 11361143.[PubMed] [CrossRef]
131. Vink C,, Rudenko G,, Seifert HS . 2011. Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev 36 : 917948.[PubMed] [CrossRef]
132. San Filippo J,, Sung P,, Klein H . 2008. Mechanism of Eukaryotic Homologous Recombination. Annu Rev Biochem 77 : 229257.[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 : 391398.[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 : 697710.[PubMed] [CrossRef]
135. Helm RA,, Seifert HS . 2009. Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria gonorrhoeae . J Bacteriol 191 : 56135621.[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 : 6878.[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 : 943960.[PubMed] [CrossRef]
138. Stohl EA,, Seifert HS . 2001. The recX gene potentiates homologous recombination in Neisseria gonorrhoeae . Mol Microbiol 40 : 13011310.[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 : 3718837197.[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 : 898905.[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 : 306311.[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 : 387395.[PubMed] [CrossRef]
144. Proudfoot C,, McCulloch R . 2005. Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation. Nucleic Acids Res 33 : 69066919.[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 : 158171.[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 : 22552261.[PubMed] [CrossRef]
148. Cahoon LA,, Seifert HS . 2009. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae . Science 325 : 764767.[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 : 20902102.[PubMed] [CrossRef]
151. Stracker TH,, Petrini JH . 2011. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 12 : 90103.[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 : 2618526193.[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 : 1121.[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 : 4518245188.[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 : 159173.[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 : 34783493.[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 : 11351154.[PubMed] [CrossRef]
159. Hill SA,, Davies JK . 2009. Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms. FEMS Microbiol Rev 33 : 521530.[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 : 316325.[PubMed] [CrossRef]
161. Ottaviani D,, Lecain M,, Sheer D . 2014. The role of microhomology in genomic structural variation. Trends Genet 30 : 8594.[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 : 2126921277.[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 : 65756584.[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 : 17731781.[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 : 16871700.[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 : 26082618.[PubMed] [CrossRef]
168. Glover L,, Jun J,, Horn D . 2011. Microhomology-mediated deletion and gene conversion in African trypanosomes. Nucleic Acids Res 39 : 13721380.[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 : 40094018.[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 : 1043810448.[PubMed] [CrossRef]
173. Barry JD . 1997. The relative significance of mechanisms of antigenic variation in African trypanosomes. Parasitol Today 13 : 212218.[PubMed] [CrossRef]
174. Barry D,, McCulloch R . 2009. Molecular microbiology: a key event in survival. Nature 459 : 172173.[PubMed] [CrossRef]
175. Keim C,, Kazadi D,, Rothschild G,, Basu U . 2013. Regulation of AID, the B-cell genome mutator. Genes Dev 27 : 117.[PubMed] [CrossRef]
176. Durkin SG,, Glover TW . 2007. Chromosome fragile sites. Annu Rev Genet 41 : 169192.[PubMed] [CrossRef]
177. Ozeri-Galai E,,