Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

Koichi Sato; Masamichi Ishiai; Kazue Toda; Satoshi Furukoshi; Akihisa Osakabe; Hiroaki Tachiwana; Yoshimasa Takizawa; Wataru Kagawa; Hiroyuki Kitao; Naoshi Dohmae; Chikashi Obuse; Hiroshi Kimura; Minoru Takata; Hitoshi Kurumizaka

doi:10.1038/emboj.2012.197

Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

Koichi Sato, Masamichi Ishiai, Kazue Toda, Satoshi Furukoshi, Akihisa Osakabe, Hiroaki Tachiwana, Yoshimasa Takizawa, Wataru Kagawa, Hiroyuki Kitao, Naoshi Dohmae, Chikashi Obuse, Hiroshi Kimura, Minoru Takata^*, Hitoshi Kurumizaka

^*Corresponding author for this work

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

54 Citations (Scopus)

Abstract

Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair.

Original language	English
Pages (from-to)	3524-3536
Number of pages	13
Journal	EMBO Journal
Volume	31
Issue number	17
DOIs	https://doi.org/10.1038/emboj.2012.197
Publication status	Published - 2012 Aug 29

Keywords

DNA repair
FANCD2
FANCI
Fanconi anaemia
histone chaperone

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
Neuroscience(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/emboj.2012.197

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title = "Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair",

abstract = "Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair.",

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author = "Koichi Sato and Masamichi Ishiai and Kazue Toda and Satoshi Furukoshi and Akihisa Osakabe and Hiroaki Tachiwana and Yoshimasa Takizawa and Wataru Kagawa and Hiroyuki Kitao and Naoshi Dohmae and Chikashi Obuse and Hiroshi Kimura and Minoru Takata and Hitoshi Kurumizaka",

year = "2012",

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doi = "10.1038/emboj.2012.197",

language = "English",

volume = "31",

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T1 - Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

AU - Sato, Koichi

AU - Ishiai, Masamichi

AU - Toda, Kazue

AU - Furukoshi, Satoshi

AU - Osakabe, Akihisa

AU - Tachiwana, Hiroaki

AU - Takizawa, Yoshimasa

AU - Kagawa, Wataru

AU - Kitao, Hiroyuki

AU - Dohmae, Naoshi

AU - Obuse, Chikashi

AU - Kimura, Hiroshi

AU - Takata, Minoru

AU - Kurumizaka, Hitoshi

PY - 2012/8/29

Y1 - 2012/8/29

N2 - Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair.

AB - Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair.

KW - DNA repair

KW - FANCD2

KW - FANCI

KW - Fanconi anaemia

KW - histone chaperone

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Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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