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hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

Richard, Derek J., Cubeddu, Liza, Urquhart, Aaron J., Bain, Amanda, Bolderson, Emma, Menon, Dinoop, White, Malcolm F., & Khanna, Kum Kum (2011) hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity. Nucleic Acids Research.

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Abstract

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.

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17 citations in Scopus
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14 citations in Web of Science®

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ID Code: 40630
Item Type: Journal Article
Keywords: hSSB1, single-stranded DNA binding protein, DSBs, MRN complex
DOI: 10.1093/nar/gkq1340
ISSN: 0305-1048
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2011 Oxford University Press
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 10 Mar 2011 09:20
Last Modified: 01 Feb 2012 00:10

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