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 language | English |
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Pages (from-to) | 3643-3651 |
Number of pages | 9 |
Journal | Nucleic Acids Research |
Volume | 39 |
Issue number | 9 |
Early online date | 11 Jan 2011 |
DOIs | |
Publication status | Published - May 2011 |
Keywords
- Replication protein-a
- Binding-protein
- Homologous recombination
- MRE11-RAD50-NBS1 COMPLEX
- Genomic stability
- S-phase
- ATM
- Activation
- MRE11
- Checkpoint