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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Baldock RA,Day M,Wilkinson OJ,Cloney R,Jeggo PA,Oliver AW,Watts FZ,Pearl LHdoi
10.1016/j.celrep.2015.10.074subject
Has Abstractpub_date
2015-12-15 00:00:00pages
2081-9issue
10issn
2211-1247pii
S2211-1247(15)01282-6journal_volume
13pub_type
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