Ku heterodimer-independent end joining in Trypanosoma brucei cell extracts relies upon sequence microhomology

Burton, P., McBride, D. J., Wilkes, J. M., Barry, J. D. and McCulloch, R. (2007) Ku heterodimer-independent end joining in Trypanosoma brucei cell extracts relies upon sequence microhomology. Eukaryotic Cell, 6(10), pp. 1773-1781. (doi:10.1128/EC.00212-07)

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Publisher's URL: http://dx.doi.org/10.1128/EC.00212-07

Abstract

DNA double-strand breaks (DSBs) are repaired primarily by two distinct pathways: homologous recombination and nonhomologous end joining (NHEJ). NHEJ has been found in all eukaryotes examined to date and has been described recently for some bacterial species, illustrating its ancestry. Trypanosoma brucei is a divergent eukaryotic protist that evades host immunity by antigenic variation, a process in which homologous recombination plays a crucial function. While homologous recombination has been examined in some detail in T. brucei, little work has been done to examine what other DSB repair pathways the parasite utilizes. Here we show that T. brucei cell extracts support the end joining of linear DNA molecules. These reactions are independent of the Ku heterodimer, indicating that they are distinct from NHEJ, and are guided by sequence microhomology. We also demonstrate bioinformatically that T. brucei, in common with other kinetoplastids, does not encode recognizable homologues of DNA ligase IV or XRCC4, suggesting that NHEJ is either absent or mechanistically diverged in these pathogens.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barry, Professor Dave and McCulloch, Professor Richard
Authors: Burton, P., McBride, D. J., Wilkes, J. M., Barry, J. D., and McCulloch, R.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Eukaryotic Cell
Publisher:American Society for Microbiology
ISSN:1535-9778
ISSN (Online):1535-9786
Published Online:10 August 2007
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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