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 and Pearl, Laurence H (2015) ATM localization and heterochromatin repair depend on Direct Interaction of the 53BP1-BRCT2 domain with γH2AX. Cell Reports, 13 (10). pp. 2081-2089. ISSN 2211-1247

[img] PDF - Published Version
Available under License Creative Commons Attribution-NonCommercial No Derivatives.

Download (3MB)
[img] PDF - Published Version
Restricted to SRO admin only
Available under License Creative Commons Attribution.

Download (74kB)

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Felicity Watts
Date Deposited: 04 Jan 2016 15:24
Last Modified: 09 Mar 2021 14:30
URI: http://sro.sussex.ac.uk/id/eprint/58864

View download statistics for this item

📧 Request an update