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

• Published in: The EMBO journal Vol. 31; no. 17; pp. 3524 - 3536
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 29.08.2012; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: Anemia; Animals; Cell Line; Chickens; Chromatin; Deoxyribonucleic acid; DNA; DNA Damage; DNA Repair; EMBO09; EMBO13; FANCD2; FANCI; Fanconi anaemia; Fanconi Anemia Complementation Group D2 Protein - genetics; Fanconi Anemia Complementation Group D2 Protein - metabolism; Fanconi Anemia Complementation Group Proteins - metabolism; Gene Knockdown Techniques; Genetic disorders; HeLa Cells; histone chaperone; Histone Chaperones - metabolism; Histones - metabolism; Humans; Molecular biology; Mutation; Nucleosomes - metabolism; Proteins; FANCI; Fanconi anaemia; FANCD2; DNA repair; histone chaperone
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2012.197

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. Unexpected nucleosome remodelling activities of FANCD2‐FANCI proteins offer new clues as to their essential yet still enigmatic functions in DNA interstrand crosslink repair.