title: Gamma-irradiated quiescent cells repair directly induced double-strand breaks but accumulate persistent double-strand breaks during subsequent DNA replication.
abstract: H2AX is expressed at very low levels in quiescent normal cells in vivo and in vitro. Such cells repair DNA double-strand breaks (DSBs) induced by γ-irradiation through a transient stabilization of H2AX. However, the resultant cells accumulate small numbers of irreparable (or persistent) DSBs via an unknown mechanism. We found that quiescent cells that had repaired DSBs directly induced by γ-rays were prone to accumulate DSBs during the subsequent DNA replication. Unlike directly induced DSBs, secondary DSBs were not efficiently repaired, although Rad51 and 53BP1 were recruited to these sites. H2AX was dramatically stabilized in response to DSBs directly caused by γ-rays, enabling γH2AX foci formation and DSB repair, whereas H2AX was barely stabilized in response to secondary DSBs, in which γH2AX foci were small and DSBs were not efficiently repaired. Our results show a pathway that leads to the persistent DSB formation after γ-irradiation.
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.|Biological Science and Technology, Tokyo University of Science, 6-1-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Minakawa
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Atsumi
authors.affiliation: Division of Integrated Protein Functions, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shinohara
authors.affiliation: Biological Science and Technology, Tokyo University of Science, 6-1-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D016475:3T3 Cells; D000818:Animals; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004261:DNA Replication / Q000235:genetics* / Q000528:radiation effects; D005347:Fibroblasts; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects; D006657:Histones / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D051135:Rad51 Recombinase / Q000096:biosynthesis / Q000235:genetics*; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D006657:Histones; D051135:Rad51 Recombinase; D000071857:Tumor Suppressor p53-Binding Protein 1; C498302:Trp53bp1 protein, mouse; C475961:gamma-H2AX protein, mouse