Barnes, R. L. and 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 Research, 35(10), pp. 3478-3493. (doi: 10.1093/nar/gkm249)
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Publisher's URL: http://dx.doi.org/10.1093/nar/gkm249
Abstract
Homologous recombination functions universally in the maintenance of genome stability through the repair of DNA breaks and in ensuring the completion of replication. In some organisms, homologous recombination can perform more specific functions. One example of this is in antigenic variation, a widely conserved mechanism for the evasion of host immunity. <i>Trypanosoma brucei</i>, the causative agent of sleeping sickness in Africa, undergoes antigenic variation by periodic changes in its variant surface glycoprotein (VSG) coat. VSG switches involve the activation of VSG genes, from an enormous silent archive, by recombination into specialized expression sites. These reactions involve homologous recombination, though they are characterized by an unusually high rate of switching and by atypical substrate requirements. Here, we have examined the substrate parameters of T. brucei homologous recombination. We show, first, that the reaction is strictly dependent on substrate length and that it is impeded by base mismatches, features shared by homologous recombination in all organisms characterized. Second, we identify a pathway of homologous recombination that acts preferentially on short substrates and is impeded to a lesser extent by base mismatches and the mismatch repair machinery. Finally, we show that mismatches during T. brucei recombination may be repaired by short-patch mismatch repair.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McCulloch, Professor Richard |
| Authors: | Barnes, R. L., and McCulloch, R. |
| Subjects: | Q Science > QH Natural history > QH345 Biochemistry |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| ISSN: | 0305-1048 |
| ISSN (Online): | 1362-4962 |
| Published Online: | 03 May 2007 |
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