title: GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination.
abstract: RAD51 is a key factor in homologous recombination (HR) and plays an essential role in cellular proliferation by repairing DNA damage during replication. The assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2. We found that human RAD51 directly binds GEMIN2/SIP1, a protein involved in spliceosome biogenesis. Biochemical analyses indicated that GEMIN2 enhances the RAD51-DNA complex formation by inhibiting RAD51 dissociation from DNA, and thereby stimulates RAD51-mediated homologous pairing. GEMIN2 also enhanced the RAD51-mediated strand exchange, when RPA was pre-bound to ssDNA before the addition of RAD51. To analyze the function of GEMIN2, we depleted GEMIN2 in the chicken DT40 line and in human cells. The loss of GEMIN2 reduced HR efficiency and resulted in a significant decrease in the number of RAD51 subnuclear foci, as observed in cells deficient in BRCA1 and BRCA2. These observations and our biochemical analyses reveal that GEMIN2 regulates HR as a novel RAD51 mediator.
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Yong
authors.initials: Y
authors.lastname: Qing
authors.forename: Motoki
authors.initials: M
authors.lastname: Takaku
authors.forename: Takako
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Morozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsujita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kogame
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Shibata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002645:Chickens; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic; D055532:SMN Complex Proteins / Q000378:metabolism*
chemical_list: D055532:SMN Complex Proteins; D004247:DNA; D051135:Rad51 Recombinase
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