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ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with ?H2AX.

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 ?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.

SUBMITTER: Baldock RA

PROVIDER: S-EPMC4688034 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Baldock Robert A RA Day Matthew M Wilkinson Oliver J OJ Cloney Ross R Jeggo Penelope A PA Oliver Antony W AW Watts Felicity Z FZ Pearl Laurence H LH

Cell reports 20151125 10

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, co ...[more]

PMID: 26628370

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