Comprehensive phenotypic analysis of knockout mice deficient in cyclin G1 and cyclin G2

• Published in: Scientific reports 2016-12, Vol.6 (1), p.39091-39091, Article 39091
• Main Authors: Ohno, Shouichi, Ikeda, Jun-ichiro, Naito, Yoko, Okuzaki, Daisuke, Sasakura, Towa, Fukushima, Kohshiro, Nishikawa, Yukihiro, Ota, Kaori, Kato, Yorika, Wang, Mian, Torigata, Kosuke, Kasama, Takashi, Uchihashi, Toshihiro, Miura, Daisaku, Yabuta, Norikazu, Morii, Eiichi, Nojima, Hiroshi
• Format: Article
• Language: English
• Subjects: 38; 38/1; 38/39; 38/61; 631/337/1427; 631/67/68; 631/67/69; Animals; Camptothecin; Camptothecin - adverse effects; Cancer; Cell cycle; Cell Line, Tumor; Cells, Cultured; Checkpoint Kinase 2 - metabolism; CHK2 protein; Cyclin G1; Cyclin G1 - genetics; Cyclin G1 - metabolism; Cyclin G2 - genetics; Cyclin G2 - metabolism; Deoxyribonucleic acid; Dephosphorylation; DNA; DNA Damage; DNA Repair; Down-Regulation; Embryo fibroblasts; Embryos; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - radiation effects; Head & neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Humanities and Social Sciences; I.R. radiation; Ionizing radiation; Mice; Mice, Knockout; multidisciplinary; Phenotype; Phosphoprotein phosphatase; Phosphorylation; Prognosis; Protein phosphatase; Radiation, Ionizing; Rodents; Science; Tumor cell lines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep39091

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.