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ATM localization and heterochromatin repair depend on Direct Interaction of the 53BP1-BRCT2 domain with ?H2AX

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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 Pearl
53BP1 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 Reports

ISSN

2211-1247

Publisher

Elsevier

Issue

10

Volume

13

Page range

2081-2089

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-04

First Open Access (FOA) Date

2016-01-04

First Compliant Deposit (FCD) Date

2015-12-16

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