Glover, L., McCulloch, R. and Horn, D. (2008) Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes. Nucleic Acids Research, 36(8), pp. 2608-2618. (doi: 10.1093/nar/gkn104)
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Publisher's URL: http://dx.doi.org/10.1093/nar/gkn104
Abstract
Genetic diversity in fungi and mammals is generated through mitotic double-strand break-repair (DSBR), typically involving homologous recombination (HR) or non-homologous end joining (NHEJ). Microhomology-mediated joining appears to serve a subsidiary function. The African trypanosome, a divergent protozoan parasite, relies upon rearrangement of subtelomeric variant surface glycoprotein (<i>VSG</i>) genes to achieve antigenic variation. Evidence suggests an absence of NHEJ but chromosomal repair remains largely unexplored. We used a system based on I-SceI meganuclease and monitored temporally constrained DSBR at a specific chromosomal site in bloodstream form <i>Trypanosoma brucei</i>. In response to the lesion, adjacent single-stranded DNA was generated; the homologous strand-exchange factor, Rad51, accumulated into foci; a G<sub>2</sub>M checkpoint was activated and > 50% of cells displayed successful repair. Quantitative analysis of DSBR pathways employed indicated that inter-chromosomal HR dominated. HR displayed a strong preference for the allelic template but also the capacity to interact with homologous sequence on heterologous chromosomes. Intra-chromosomal joining was predominantly, and possibly exclusively, microhomology mediated, a situation unique among organisms examined to date. These DSBR pathways available to <i>T. brucei</i> likely underlie patterns of antigenic variation and the evolution of the vast <i>VSG</i> gene family
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McCulloch, Professor Richard and Horn, Mr David |
| Authors: | Glover, L., McCulloch, R., and Horn, D. |
| Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| ISSN: | 0305-1048 |
| ISSN (Online): | 1362-4962 |
| Published Online: | 11 March 2008 |
| Related URLs: |
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