title: Roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome replication.
abstract: The nucleosome, which is composed of DNA wrapped around a histone octamer, is a fundamental unit of chromatin and is duplicated during the eukaryotic DNA replication process. The evolutionarily conserved histone chaperone cell cycle gene 1 (CCG1) interacting factor A/anti-silencing function 1 (CIA/Asf1) is involved in histone transfer and nucleosome reassembly during DNA replication. CIA/Asf1 has been reported to split the histone (H3-H4)(2)  tetramer into histone H3-H4 dimer(s) in vitro, raising a possibility that, in DNA replication, CIA/Asf1 is involved in nucleosome disassembly and the promotion of semi-conservative histone H3-H4 dimer deposition onto each daughter strand in vivo. Despite numerous studies on the functional roles of CIA/Asf1, its mechanistic role(s) remains elusive because of lack of biochemical analyses. The biochemical studies described here show that a V94R CIA/Asf1 mutant, which lacks histone (H3-H4)(2)  tetramer splitting activity, does not form efficiently a quaternary complex with histones H3-H4 and the minichromosome maintenance 2 (Mcm2) subunit of the Mcm2-7 replicative DNA helicase. Interestingly, the mutant enhances nascent DNA strand synthesis in a cell-free chromosomal DNA replication system using Xenopus egg extracts. These results suggest that CIA/Asf1 in the CIA/Asf1-H3-H4-Mcm2 complex, which is considered to be an intermediate in histone transfer during DNA replication, negatively regulates the progression of the replication fork.
authors: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, Japan.
authors: Katsuyuki
authors: K
authors: Ishikawa
authors: Tatsuya
authors: T
authors: Ohsumi
authors: Shusuke
authors: S
authors: Tada
authors: Ryo
authors: R
authors: Natsume
authors: Lena Rani
authors: LR
authors: Kundu
authors: Naohito
authors: N
authors: Nozaki
authors: Toshiya
authors: T
authors: Senda
authors: Takemi
authors: T
authors: Enomoto
authors: Masami
authors: M
authors: Horikoshi
authors: Masayuki
authors: M
authors: Seki
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication / Q000502:physiology*; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D014981:Xenopus
chemical_list: D056488:Histone Chaperones; D006657:Histones; D009707:Nucleosomes