Machado, C. R. et al. (2014) Nucleotide excision repair in Trypanosoma brucei: specialization of transcription-coupled repair due to multigenic transcription. Molecular Microbiology, 92(4), pp. 756-776. (doi: 10.1111/mmi.12589) (PMID:24661334) (PMCID:PMC4138998)
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Abstract
Nucleotide excision repair (NER) is a highly conserved genome repair pathway acting on helix distorting DNA lesions. NER is divided into two sub-pathways: global genome NER (GG-NER), which is responsible for repair throughout genomes, and transcription-coupled NER (TC-NER), which acts on lesions that impede transcription. The extent of the <i>Trypanosoma brucei</i> genome that is transcribed is highly unusual, since most genes are organised in multigene transcription units, each transcribed from a single promoter. Given this transcription organisation, we have addressed the importance of NER to <i>T. brucei</i> genome maintenance by performing RNAi against all predicted contributing factors. Our results indicate that TC-NER is the main pathway of NER repair, but only CSB, XPBz and XPG contribute. Moreover, we show that UV lesions are inefficiently repaired in <i>T. brucei</i>, perhaps due to preferential use of RNA polymerase translesion synthesis. RNAi of XPC and DDB was found to be lethal, and we show that these factors act in inter-strand crosslink repair. XPD and XPB appear only to act in transcription, not repair. This work indicates that the predominance of multigenic transcription in <i>T. brucei</i> has resulted in pronounced adaptation of NER relative to the host and may be an attractive drug target.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Marcello, Dr Lucio and De Almeida Marques, Dr Catarina and Mendes, Ms Isabela and Machado, Professor Carlos and McCulloch, Professor Richard |
| Authors: | Machado, C. R., Vieira-da-Rocha, J. P., Mendes, I. C., Rajão, M. A., Marcello, L., Bitar, M., Drummond, M. G., Grynberg, P., Oliveira, D. A.A., Marques, C., Van Houten, B., and McCulloch, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Molecular Microbiology |
| Publisher: | Wiley |
| ISSN: | 0950-382X |
| ISSN (Online): | 1365-2958 |
| Published Online: | 25 March 2014 |
| Copyright Holders: | Copyright © 2014 The Authors |
| First Published: | First published in Molecular Microbiology 92(4):756-776 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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