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

Robert A Baldock, Matthew Day, Oliver J Wilkinson, Ross Cloney, Penelope A Jeggo, Antony W Oliver, Felicity Z Watts, Laurence H Pearl

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2081-9
Number of pages9
JournalCell Reports
Volume13
Issue number10
DOIs
Publication statusPublished - 15 Dec 2015
Externally publishedYes

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Heterochromatin
Automatic teller machines
DNA Damage
Repair
Double-Stranded DNA Breaks
DNA
Post Translational Protein Processing
DNA Repair
Histones
Phosphorylation
Peptides
Proteins

Cite this

Baldock, Robert A ; Day, Matthew ; Wilkinson, Oliver J ; Cloney, Ross ; Jeggo, Penelope A ; Oliver, Antony W ; Watts, Felicity Z ; Pearl, Laurence H. / ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX. In: Cell Reports. 2015 ; Vol. 13, No. 10. pp. 2081-9.
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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.",
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Baldock, RA, Day, M, Wilkinson, OJ, Cloney, R, Jeggo, PA, Oliver, AW, Watts, FZ & Pearl, LH 2015, 'ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX' Cell Reports, vol. 13, no. 10, pp. 2081-9. https://doi.org/10.1016/j.celrep.2015.10.074

ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX. / Baldock, Robert A; Day, Matthew; Wilkinson, Oliver J; Cloney, Ross; Jeggo, Penelope A; Oliver, Antony W; Watts, Felicity Z; Pearl, Laurence H.

In: Cell Reports, Vol. 13, No. 10, 15.12.2015, p. 2081-9.

Research output: Contribution to journalArticle

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AU - Day, Matthew

AU - Wilkinson, Oliver J

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AU - Jeggo, Penelope A

AU - Oliver, Antony W

AU - Watts, Felicity Z

AU - Pearl, Laurence H

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