title: Histone acetyltransferase 1 is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells.
abstract: Histone acetyltransferase 1 (HAT1) is implicated for diacetylation of Lys-5 and Lys-12 of newly synthesized histone H4, the biological significance of which remains unclear. To investigate the in vivo role of HAT1, we generated HAT1-deficient DT40 clone (HAT1(-/-)). HAT1(-/-) cells exhibited greatly reduced diacetylation levels of Lys-5 and Lys-12, and acetylation level of Lys-5 of cytosolic and chromatin histones H4, respectively. The in vitro nucleosome assembly assay and in vivo MNase digestion assay revealed that HAT1 and diacetylation of Lys-5 and Lys-12 of histone H4 are dispensable for replication-coupled chromatin assembly. HAT1(-/-) cells had mild growth defect, conferring sensitivities to methyl methanesulfonate and camptothecin that enforce replication blocks creating DNA double strand breaks. Such heightened sensitivities were associated with prolonged late-S/G2 phase. These results indicate that HAT1 participates in recovering replication block-mediated DNA damages, probably through chromatin modulation based on acetylation of Lys-5 and Lys-12 of histone H4.
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Miyazaki Medical College, Japan.
authors.forename: Hirak Kumar
authors.initials: HK
authors.lastname: Barman
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ono
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishijima
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Sanematsu
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Shibahara
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000107:Acetylation; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008856:Microscopy, Fluorescence; D009154:Mutation; D016196:S Phase / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002843:Chromatin; D006657:Histones; D008741:Methyl Methanesulfonate; D051548:Histone Acetyltransferases; D008239:Lysine; D002166:Camptothecin