Journal article
Linking DNA repair and cell cycle progression through serine ADP-ribosylation of histones
- Abstract:
- Although serine ADP-ribosylation (Ser-ADPr) by Poly(ADP-ribose)-polymerases is a cornerstone of the DNA damage response, how this regulates DNA repair and genome stability is unknown. Here, we exploit the ability to manipulate histone genes in Dictyostelium to identify that ADPr of the histone variant H3b at S10 and S28 maintains genome stability by integrating double strand break (DSB) repair with mitotic entry. Given the critical requirement for mitotic H3S10/28 phosphorylation, we develop separation of function mutations that maintain S10 phosphorylation whilst disrupting ADPr. Mechanistically, this reveals a requirement for H3bS10/28 ADPr in non-homologous end-joining by recruiting Ku to DSBs. Moreover, this also identifies H3bS10/S28 ADPr is critical to prevent premature mitotic entry with unresolved DNA damage, thus maintaining genome stability. Together, these data demonstrate how serine ADPr of histones coordinates DNA repair with cell cycle progression to maintain genome stability.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 2.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-021-27867-4
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 13
- Article number:
- 185
- Publication date:
- 2022-01-13
- Acceptance date:
- 2021-12-19
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
-
1226065
- Local pid:
-
pubs:1226065
- Deposit date:
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2021-12-20
Terms of use
- Copyright holder:
- Brustel et al.
- Copyright date:
- 2022
- Rights statement:
- ©2022 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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