ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX

Robert A Baldock, Matthew Day, Oliver J Wilkinson, Ross Cloney, Penelope A Jeggo, Antony W Oliver, Felicity Z Watts, Laurence H Pearl

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2081-9
Number of pages9
JournalCell Reports
Volume13
Issue number10
DOIs
Publication statusPublished - 15 Dec 2015
Externally publishedYes

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