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

被引：54

作者：

Sato, Koichi ^{[2
]}

Ishiai, Masamichi

Toda, Kazue ^{[2
]}

Furukoshi, Satoshi ^{[2
]}

Osakabe, Akihisa ^{[2
]}

Tachiwana, Hiroaki ^{[2
]}

Takizawa, Yoshimasa ^{[2
]}

Kagawa, Wataru ^{[2
]}

Kitao, Hiroyuki ^{[3
]}

Dohmae, Naoshi ^{[4
]}

Obuse, Chikashi ^{[5
]}

Kimura, Hiroshi ^{[6
]}

Takata, Minoru ^{[1
]}

Kurumizaka, Hitoshi ^{[2
]}

机构：

[1] Kyoto Univ, Ctr Radiat Biol, Lab DNA Damage Signaling, Dept Late Effects Studies,Sakyo Ku, Kyoto 6068501, Japan

[2] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Tokyo, Japan

[3] Kyushu Univ, Dept Mol Oncol, Grad Sch Med Sci, Fukuoka 812, Japan

[4] RIKEN Adv Sci Inst, Saitama, Japan

[5] Hokkaido Univ, Grad Sch Life Sci, Sapporo, Hokkaido 060, Japan

[6] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan

来源：

EMBO JOURNAL | 2012年 / 31卷 / 17期

关键词：

DNA repair; FANCD2; FANCI; Fanconi anaemia; histone chaperone; HOLLIDAY JUNCTION RESOLVASE; CENP-A; CORE-COMPLEX; HOMOLOGOUS RECOMBINATION; MONOUBIQUITINATED FANCD2; NUCLEOSOME FORMATION; STRUCTURAL BASIS; PATHWAY; CELLS; SLX4;

D O I：

10.1038/emboj.2012.197

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. The EMBO Journal (2012) 31, 3524-3536. doi: 10.1038/emboj.2012.197; Published online 24 July 2012 Subject Categories: genome stability & dynamics; chromatin & transcription

引用

页码：3524 / 3536

页数：13

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