The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin Journal Article
| Authors: | Dhingra, N.; Kuppa, S.; Wei, L.; Pokhrel, N.; Baburyan, S.; Meng, X.; Antony, E.; Zhao, X. |
| Article Title: | The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin |
| Abstract: | The DNA damage checkpoint induces many cellular changes to cope with genotoxic stress. However, persistent checkpoint signaling can be detrimental to growth partly due to blockage of cell cycle resumption. Checkpoint dampening is essential to counter such harmful effects, but its mechanisms remain to be understood. Here, we show that the DNA helicase Srs2 removes a key checkpoint sensor complex, RPA, from chromatin to down-regulate checkpoint signaling in budding yeast. The Srs2 and RPA antagonism is supported by their numerous suppressive genetic interactions. Importantly, moderate reduction of RPA binding to single-strand DNA (ssDNA) rescues hypercheckpoint signaling caused by the loss of Srs2 or its helicase activity. This rescue correlates with a reduction in the accumulated RPA and the associated checkpoint kinase on chromatin in srs2 mutants. Moreover, our data suggest that Srs2 regulation of RPA is separable from its roles in recombinational repair and critically contributes to genotoxin resistance. We conclude that dampening checkpoint by Srs2-mediated RPA recycling from chromatin aids cellular survival of genotoxic stress and has potential implications in other types of DNA transactions. © 2021 National Academy of Sciences. All rights reserved. |
| Keywords: | recombinational repair; genotoxic stress; srs2; checkpoint dampening; rpa regulation |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 118 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2021-02-23 |
| Start Page: | e2020185118 |
| Language: | English |
| DOI: | 10.1073/pnas.2020185118 |
| PUBMED: | 33602817 |
| PROVIDER: | scopus |
| PMCID: | PMC7923681 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work