Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes

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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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
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 > Institute of Infection Immunity and Inflammation
Journal Name:Nucleic Acids Research
Publisher:Oxford University Press
ISSN (Online):1362-4962
Published Online:11 March 2008
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
401101DNA recombination pathways and antigenic variation in trypanosoma bruceiRichard McCullochMedical Research Council (MRC)G0401553Infection Immunity and Inflammation Life Sciences