PIIS2211124715012826.pdf (3.14 MB)
ATM localization and heterochromatin repair depend on Direct Interaction of the 53BP1-BRCT2 domain with ?H2AX
journal contribution
posted on 2023-06-08, 23:46 authored by Robert A Baldock, Matthew Day, Oliver J Wilkinson, Ross Cloney, Penny Jeggo, Antony OliverAntony Oliver, Felicity Watts, Laurence PearlLaurence Pearl53BP1 plays multiple roles in mammalian DNA damage repair, mediating pathway choice and facilitating DNA double-strand break repair in heterochromatin. Although it possesses a C-terminal BRCT2 domain, commonly involved in phospho-peptide binding in other proteins, initial recruitment of 53BP1 to sites of DNA damage depends on interaction with histone post-translational modifications-H4K20me2 and H2AK13/K15ub-downstream of the early ?H2AX phosphorylation mark of DNA damage. We now show that, contrary to current models, the 53BP1-BRCT2 domain binds ?H2AX directly, providing a third post-translational mark regulating 53BP1 function. We find that the interaction of 53BP1 with ?H2AX is required for sustaining the 53BP1-dependent focal concentration of activated ATM that facilitates repair of DNA double-strand breaks in heterochromatin in G1.
History
Publication status
- Published
File Version
- Published version
Journal
Cell ReportsISSN
2211-1247Publisher
ElsevierExternal DOI
Issue
10Volume
13Page range
2081-2089Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-04First Open Access (FOA) Date
2016-01-04First Compliant Deposit (FCD) Date
2015-12-16Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC