title: Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.
abstract: The Bloom syndrome gene product, BLM, is a member of the highly conserved RecQ family. An emerging concept is the BLM helicase collaborates with the homologous recombination (HR) machinery to help avoid undesirable HR events and to achieve a high degree of fidelity during the HR reaction. However, exactly how such coordination occurs in vivo is poorly understood. Here, we identified a protein termed SPIDR (scaffolding protein involved in DNA repair) as the link between BLM and the HR machinery. SPIDR independently interacts with BLM and RAD51 and promotes the formation of a BLM/RAD51-containing complex of biological importance. Consistent with its role as a scaffolding protein for the assembly of BLM and RAD51 foci, cells depleted of SPIDR show increased rate of sister chromatid exchange and defects in HR. Moreover, SPIDR depletion leads to genome instability and causes hypersensitivity to DNA damaging agents. We propose that, through providing a scaffold for the cooperation of BLM and RAD51 in a multifunctional DNA-processing complex, SPIDR not only regulates the efficiency of HR, but also dictates the specific HR pathway.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.forename: Jinhua
authors.initials: J
authors.lastname: Han
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Shunli
authors.initials: S
authors.lastname: Dong
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
mesh_terms: D001816:Bloom Syndrome / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053484:RecQ Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059767:Recombinational DNA Repair / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011994:Recombinant Proteins; C582833:SPIDR protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C097151:Bloom syndrome protein; D053484:RecQ Helicases
keywords: DNA double-strand breaks; double Holliday junction; noncrossover