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

Derek J. Richard, Liza Cubeddu, Aaron J. Urquhart, Amanda Bain, Emma Bolderson, Dinoop Menon, Malcolm F. White, Kum Kum Khanna

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3643-3651
Number of pages9
JournalNucleic Acids Research
Volume39
Issue number9
Early online date11 Jan 2011
DOIs
Publication statusPublished - May 2011

Keywords

  • Replication protein-a
  • Binding-protein
  • Homologous recombination
  • MRE11-RAD50-NBS1 COMPLEX
  • Genomic stability
  • S-phase
  • ATM
  • Activation
  • MRE11
  • Checkpoint

Fingerprint

Dive into the research topics of 'hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity'. Together they form a unique fingerprint.

Cite this