Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery.
Cyclin G1 is one of the target genes of the transcription factor p53, and is induced in a p53-dependent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena, its precise function remains unclear. Here we present an analysis of the physiological role of cyclin G1 using mice homozygous for a targeted disruption of the cyclin G1 gene. In order to clarify the role of cyclin G1 in the p53 pathway, downstream events such as apoptosis, cell growth and cell cycle checkpoint control were analysed in thymocytes and embryonic fibroblasts derived from cyclin G1-disrupted mice. No difference was detected in induction of apoptosis between mouse embryo fibroblasts (MEFs) derived from cyclin G1+/+ and cyclin G1-/- mice. Following irradiation, cyclin G1-/- MEFs proliferated more slowly and reached lower cell densities in culture dishes than cyclin G1+/+ MEFs. Analysis of cell survival showed that cyclin G1-/- MEFs were about twice as sensitive as cyclin G1+/+ MEFs to gamma radiation or UV radiation. Cyclin G1-/- mice were more sensitive to gamma radiation than wild-type mice. Flow cytometeric analysis revealed that the number of cyclin G1-/- MEFs in G2/M phase after irradiation was reduced by 50% relative to cyclin G1+/+ MEFs. Our results demonstrate that cyclin G1 plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress.
Kimura
S H
SH
Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ikawa
M
M
Ito
A
A
Okabe
M
M
Nojima
H
H
D000818:Animals; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase; D005720:Gamma Rays; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis; D016254:Mutagenesis, Insertional; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D014916:Whole-Body Irradiation
C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D016159:Tumor Suppressor Protein p53