Comprehensive Phenotypic Analysis of Knockout Mice Deficient in Cyclin G1 and Cyclin G2

Overview

Journal Sci Rep

Specialty Science

Date 2016 Dec 17

PMID 27982046

Citations 9

Authors

Shouichi Ohno

Jun-Ichiro Ikeda

Yoko Naito

Daisuke Okuzaki

Towa Sasakura

Kohshiro Fukushima

Yukihiro Nishikawa

Kaori Ota

Yorika Kato

Mian Wang

Kosuke Torigata

Takashi Kasama

Toshihiro Uchihashi

Daisaku Miura

Norikazu Yabuta

Eiichi Morii

Hiroshi Nojima

Affiliations

Soon will be listed here.

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.

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