Black, J. A., Crouch, K. , Lemgruber, L. , Lapsley, C., Dickens, N. , Tosi, L. R.O., Mottram, J. C. and McCulloch, R. (2020) Trypanosoma brucei ATR links DNA damage signalling during antigenic variation with regulation of RNA Polymerase I-transcribed surface antigens. Cell Reports, 30(3), 836-851.e5. (doi: 10.1016/j.celrep.2019.12.049) (PMID:31968257) (PMCID:PMC6988115)
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Abstract
Trypanosoma brucei evades mammalian immunity by using recombination to switch its surface-expressed variant surface glycoprotein (VSG), while ensuring that only one of many subtelomeric multigene VSG expression sites are transcribed at a time. DNA repair activities have been implicated in the catalysis of VSG switching by recombination, not transcriptional control. How VSG switching is signaled to guide the appropriate reaction or to integrate switching into parasite growth is unknown. Here, we show that the loss of ATR, a DNA damage-signaling protein kinase, is lethal, causing nuclear genome instability and increased VSG switching through VSG-localized damage. Furthermore, ATR loss leads to the increased transcription of silent VSG expression sites and expression of mixed VSGs on the cell surface, effects that are associated with the altered localization of RNA polymerase I and VEX1. This work shows that ATR acts in antigenic variation both through DNA damage signaling and surface antigen expression control.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dickens, Dr Nicholas and Crouch, Dr Kathryn and Black, Dr Jennifer Ann and Lemgruber Soares, Dr Leandro and Lapsley, Mr Craig and McCulloch, Professor Richard and Mottram, Professor Jeremy |
| Authors: | Black, J. A., Crouch, K., Lemgruber, L., Lapsley, C., Dickens, N., Tosi, L. R.O., Mottram, J. C., and McCulloch, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Cell Reports |
| Publisher: | Elsevier |
| ISSN: | 2211-1247 |
| ISSN (Online): | 2211-1247 |
| Published Online: | 21 January 2020 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Cell Reports 30(3):836-851.e5 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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