GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination

Yoshimasa Takizawa; Yong Qing; Motoki Takaku; Takako Ishida; Yuichi Morozumi; Takashi Tsujita; Toshiaki Kogame; Kouji Hirota; Masayuki Takahashi; Takehiko Shibata; Hitoshi Kurumizaka; Shunichi Takeda

doi:10.1093/nar/gkq271

GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination

Yoshimasa Takizawa, Yong Qing, Motoki Takaku, Takako Ishida, Yuichi Morozumi, Takashi Tsujita, Toshiaki Kogame, Kouji Hirota, Masayuki Takahashi, Takehiko Shibata, Hitoshi Kurumizaka, Shunichi Takeda^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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 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 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.

Original language	English
Article number	gkq271
Pages (from-to)	5059-5074
Number of pages	16
Journal	Nucleic Acids Research
Volume	38
Issue number	15
DOIs	https://doi.org/10.1093/nar/gkq271
Publication status	Published - 2010 Apr 19

ASJC Scopus subject areas

Genetics

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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 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 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.",

author = "Yoshimasa Takizawa and Yong Qing and Motoki Takaku and Takako Ishida and Yuichi Morozumi and Takashi Tsujita and Toshiaki Kogame and Kouji Hirota and Masayuki Takahashi and Takehiko Shibata and Hitoshi Kurumizaka and Shunichi Takeda",

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AU - Takizawa, Yoshimasa

AU - Qing, Yong

AU - Takaku, Motoki

AU - Ishida, Takako

AU - Morozumi, Yuichi

AU - Tsujita, Takashi

AU - Kogame, Toshiaki

AU - Hirota, Kouji

AU - Takahashi, Masayuki

AU - Shibata, Takehiko

AU - Kurumizaka, Hitoshi

AU - Takeda, Shunichi

PY - 2010/4/19

Y1 - 2010/4/19

N2 - 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 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 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.

AB - 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 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 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.

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GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination

Abstract

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