title: hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity.
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.
authors.affiliation: Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia. derekR@qimr.edu.au
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Richard
authors.forename: Liza
authors.initials: L
authors.lastname: Cubeddu
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Urquhart
authors.forename: Amanda
authors.initials: A
authors.lastname: Bain
authors.forename: Emma
authors.initials: E
authors.lastname: Bolderson
authors.forename: Dinoop
authors.initials: D
authors.lastname: Menon
authors.forename: Malcolm F
authors.initials: MF
authors.lastname: White
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
mesh_terms: D017766:Acid Anhydride Hydrolases; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D000076228:MRE11 Homologue Protein; D024101:Mitochondrial Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D024101:Mitochondrial Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C504091:NABP2 protein, human; D004706:Endodeoxyribonucleases; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes