ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX.
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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.
Intracellular Signaling Peptides and Proteins
Chromosomal Proteins, Non-Histone
RNA, Small Interfering
Fluorescent Antibody Technique
Protein Processing, Post-Translational
Protein Structure, Quaternary
DNA Breaks, Double-Stranded
Gene Knockdown Techniques
Ataxia Telangiectasia Mutated Proteins
Tumor Suppressor p53-Binding Protein 1
License start date
Cell reports, 2015, 13 (10), pp. 2081 - 2089
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0
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