ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX.
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Date
2015-12-15ICR Author
Author
Baldock, RA
Day, M
Wilkinson, OJ
Cloney, R
Jeggo, PA
Oliver, AW
Watts, FZ
Pearl, LH
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Heterochromatin
Animals
Humans
Mice
Intracellular Signaling Peptides and Proteins
DNA-Binding Proteins
Chromosomal Proteins, Non-Histone
Histones
RNA, Small Interfering
Fluorescent Antibody Technique
Crystallography, X-Ray
Transfection
DNA Repair
Protein Processing, Post-Translational
Protein Structure, Quaternary
DNA Breaks, Double-Stranded
Gene Knockdown Techniques
Ataxia Telangiectasia Mutated Proteins
Tumor Suppressor p53-Binding Protein 1
Language
eng
Date accepted
2015-10-26
License start date
2015-12
Citation
Cell reports, 2015, 13 (10), pp. 2081 - 2089
Publisher
CELL PRESS
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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