TY - JOUR
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.
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U2 - 10.1038/emboj.2012.197
DO - 10.1038/emboj.2012.197
M3 - Article
C2 - 22828868
AN - SCOPUS:84866121561
VL - 31
SP - 3524
EP - 3536
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 17
ER -
