title: Comprehensive phenotypic analysis of knockout mice deficient in cyclin G1 and cyclin G2.
abstract: Cyclin G1 (CycG1) and Cyclin G2 (CycG2) play similar roles during the DNA damage response (DDR), but their detailed roles remain elusive. To investigate their distinct roles, we generated knockout mice deficient in CycG1 (G1KO) or CycG2 (G2KO), as well as double knockout mice (DKO) deficient in both proteins. All knockouts developed normally and were fertile. Generation of mouse embryonic fibroblasts (MEFs) from these mice revealed that G2KO MEFs, but not G1KO or DKO MEFs, were resistant to DNA damage insults caused by camptothecin and ionizing radiation (IR) and underwent cell cycle arrest. CycG2, but not CycG1, co-localized with γH2AX foci in the nucleus after γ-IR, and γH2AX-mediated DNA repair and dephosphorylation of CHK2 were delayed in G2KO MEFs. H2AX associated with CycG1, CycG2, and protein phosphatase 2A (PP2A), suggesting that γH2AX affects the function of PP2A via direct interaction with its B'γ subunit. Furthermore, expression of CycG2, but not CycG1, was abnormal in various cancer cell lines. Kaplan-Meier curves based on TCGA data disclosed that head and neck cancer patients with reduced CycG2 expression have poorer clinical prognoses. Taken together, our data suggest that reduced CycG2 expression could be useful as a novel prognostic marker of cancer.
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Pathology, Graduate School of Medicine, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Jun-Ichiro
authors.initials: JI
authors.lastname: Ikeda
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Towa
authors.initials: T
authors.lastname: Sasakura
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kohshiro
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishikawa
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ota
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yorika
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Torigata
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kasama
authors.affiliation: First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Uchihashi
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Miura
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yabuta
authors.affiliation: Department of Pathology, Graduate School of Medicine, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000009:adverse effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D056766:Cyclin G1 / Q000235:genetics* / Q000378:metabolism; D056767:Cyclin G2 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010766:Phosphorylation; D011839:Radiation, Ionizing
chemical_list: C534703:Ccng1 protein, mouse; D056766:Cyclin G1; D056767:Cyclin G2; D064447:Checkpoint Kinase 2; C578633:Chek2 protein, mouse; D002166:Camptothecin