ATM localization and heterochromatin repair depend on direct interaction of the 53BP1-BRCT 2 domain with γH2AX

Baldock, Robert A ORCID: 0000-0002-4649-2966, Day, Matthew, Wilkinson, Oliver J, Cloney, Ross, Jeggo, Penelope A, Oliver, Antony W, Watts, Felicity Z and Pearl, Laurence H (2015) ATM localization and heterochromatin repair depend on direct interaction of the 53BP1-BRCT 2 domain with γH2AX. Cell Reports, 13 (10). pp. 2081-2089. doi:10.1016/j.celrep.2015.10.074

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Abstract

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 γH2AX phosphorylation mark of DNA damage. We now show that, contrary to current models, the 53BP1-BRCT2 domain binds γH2AX directly, providing a third post-translational mark regulating 53BP1 function. We find that the interaction of 53BP1 with γH2AX is required for sustaining the 53BP1-dependent focal concentration of activated ATM that facilitates repair of DNA double-strand breaks in heterochromatin in G1.

Item Type: Article
Article Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
Divisions: Schools and Research Institutes > School of Natural & Social Sciences > Environmental Sciences
Research Priority Areas: Environmental Dynamics & Governance
Depositing User: Robbie Baldock
Date Deposited: 10 Jun 2021 13:45
Last Modified: 10 Jun 2021 14:00
URI: http://eprints.glos.ac.uk/id/eprint/9782

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