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.
authors: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors: Koichi
authors: K
authors: Sato
authors: Masamichi
authors: M
authors: Ishiai
authors: Kazue
authors: K
authors: Toda
authors: Satoshi
authors: S
authors: Furukoshi
authors: Akihisa
authors: A
authors: Osakabe
authors: Hiroaki
authors: H
authors: Tachiwana
authors: Yoshimasa
authors: Y
authors: Takizawa
authors: Wataru
authors: W
authors: Kagawa
authors: Hiroyuki
authors: H
authors: Kitao
authors: Naoshi
authors: N
authors: Dohmae
authors: Chikashi
authors: C
authors: Obuse
authors: Hiroshi
authors: H
authors: Kimura
authors: Minoru
authors: M
authors: Takata
authors: Hitoshi
authors: H
authors: Kurumizaka
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D004249:DNA Damage; D004260:DNA Repair; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism
chemical_list: C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D056488:Histone Chaperones; D006657:Histones; D009707:Nucleosomes