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

Faculty of Medical Sciences

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

45 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 - Aug 29 2012

All Science Journal Classification (ASJC) codes

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

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Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair. / Sato, Koichi; Ishiai, Masamichi; Toda, Kazue; Furukoshi, Satoshi; Osakabe, Akihisa; Tachiwana, Hiroaki; Takizawa, Yoshimasa; Kagawa, Wataru; Kitao, Hiroyuki; Dohmae, Naoshi; Obuse, Chikashi; Kimura, Hiroshi; Takata, Minoru; Kurumizaka, Hitoshi.

In: EMBO Journal, Vol. 31, No. 17, 29.08.2012, p. 3524-3536.

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

Sato, Koichi ; Ishiai, Masamichi ; Toda, Kazue ; Furukoshi, Satoshi ; Osakabe, Akihisa ; Tachiwana, Hiroaki ; Takizawa, Yoshimasa ; Kagawa, Wataru ; Kitao, Hiroyuki ; Dohmae, Naoshi ; Obuse, Chikashi ; Kimura, Hiroshi ; Takata, Minoru ; Kurumizaka, Hitoshi. / Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair. In: EMBO Journal. 2012 ; Vol. 31, No. 17. pp. 3524-3536.

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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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