Skip Navigation


Nucleic Acids Research Advance Access originally published online on March 11, 2008
Nucleic Acids Research 2008 36(8):2608-2618; doi:10.1093/nar/gkn104
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (6058K) Freely available
Right arrow Screen PDF (658K) Freely available
Right arrowOA All Versions of this Article:
36/8/2608    most recent
gkn104v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Glover, L.
Right arrow Articles by Horn, D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Glover, L.
Right arrow Articles by Horn, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2008, Vol. 36, No. 8 2608-2618
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

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

Lucy Glover1, Richard McCulloch2 and David Horn1,*

1London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT and 2Glasgow Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, Scotland, UK

*To whom correspondence should be addressed. Tel: +44 20 7927 2352; Fax: +44 20 7636 8739; Email: david.horn{at}lshtm.ac.uk

Received January 10, 2008. Revised February 20, 2008. Accepted February 25, 2008.

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 (VSG) 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 Trypanosoma brucei. In response to the lesion, adjacent single-stranded DNA was generated; the homologous strand-exchange factor, Rad51, accumulated into foci; a G2M 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 T. brucei likely underlie patterns of antigenic variation and the evolution of the vast VSG gene family.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.