ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX.
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Embargo End Date
ICR Authors
Authors
Baldock, RA
Day, M
Wilkinson, OJ
Cloney, R
Jeggo, PA
Oliver, AW
Watts, FZ
Pearl, LH
Day, M
Wilkinson, OJ
Cloney, R
Jeggo, PA
Oliver, AW
Watts, FZ
Pearl, LH
Document Type
Journal Article
Date
2015-12-15
Date Accepted
2015-10-26
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.
Citation
Cell reports, 2015, 13 (10), pp. 2081 - 2089
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247