title: MRE11 complex links RECQ5 helicase to sites of DNA damage.
abstract: RECQ5 DNA helicase suppresses homologous recombination (HR) possibly through disruption of RAD51 filaments. Here, we show that RECQ5 is constitutively associated with the MRE11-RAD50-NBS1 (MRN) complex, a primary sensor of DNA double-strand breaks (DSBs) that promotes DSB repair and regulates DNA damage signaling via activation of the ATM kinase. Experiments with purified proteins indicated that RECQ5 interacts with the MRN complex through both MRE11 and NBS1. Functional assays revealed that RECQ5 specifically inhibited the 3'-->5' exonuclease activity of MRE11, while MRN had no effect on the helicase activity of RECQ5. At the cellular level, we observed that the MRN complex was required for the recruitment of RECQ5 to sites of DNA damage. Accumulation of RECQ5 at DSBs was neither dependent on MDC1 that mediates binding of MRN to DSB-flanking chromatin nor on CtIP that acts in conjunction with MRN to promote resection of DSBs for repair by HR. Collectively, these data suggest that the MRN complex recruits RECQ5 to sites of DNA damage to regulate DNA repair.
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Functional Genomics Center Zurich, UZH/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Kanagaraj
authors.forename: Boris
authors.initials: B
authors.lastname: Mihaljevic
authors.forename: Sybille
authors.initials: S
authors.lastname: Schwendener
authors.forename: Alessandro A
authors.initials: AA
authors.lastname: Sartori
authors.forename: Bertran
authors.initials: B
authors.lastname: Gerrits
authors.forename: Igor
authors.initials: I
authors.lastname: Shevelev
authors.forename: Pavel
authors.initials: P
authors.lastname: Janscak
mesh_terms: D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000378:metabolism; D053484:RecQ Helicases / Q000032:analysis / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D005090:Exodeoxyribonucleases; D000076228:MRE11 Homologue Protein; D053484:RecQ Helicases