ATM localization and heterochromatin repair depend on Direct Interaction of the 53BP1-BRCT2 domain with γH2AX

Baldock, Robert A, 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-BRCT2 domain with γH2AX. Cell Reports, 13 (10). pp. 2081-2089. ISSN 2211-1247

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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
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Felicity Watts
Date Deposited: 04 Jan 2016 15:24
Last Modified: 04 Jan 2016 15:24
URI: http://sro.sussex.ac.uk/id/eprint/58864

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