Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery
Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery
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DOI：
10.1038/sj.onc.1204270
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发表时间：
2001-05-31
期刊：
影响因子：
8
通讯作者：
Nojima, H
中科院分区：
文献类型：
--
作者：
Kimura, SH;Ikawa, M;Nojima, H
细胞周期蛋白G1是转录因子P53的靶基因之一，在DNA损伤时以依赖于P53的方式被诱导。尽管细胞周期蛋白G1与一系列生物现象有关，但其确切的功能仍不清楚。在这里，我们使用纯合子的小鼠来分析细胞周期蛋白Ct的生理作用，目的是有针对性地破坏细胞周期蛋白G1基因。为了阐明细胞周期蛋白G1在p53通路中的作用，我们分析了细胞周期蛋白G1干扰小鼠的胸腺细胞和胚胎成纤维细胞的下游事件，如细胞凋亡、细胞生长和细胞周期检查点控制。细胞周期蛋白G1(+/+)和细胞周期蛋白G1(-/-)小鼠的胚胎成纤维细胞(MEF)在诱导细胞凋亡方面无明显差异。照射后，细胞周期蛋白G1(-/-)MEF在培养皿中的增殖速度和细胞密度均低于Cyclin G1(+/+)MEF，细胞存活率分析显示，Cyclin G1(-/-)MEF对伽马辐射或紫外线辐射的敏感性约为Cyclin G1(+/+)MEF的两倍。细胞周期蛋白G1(-/-)小鼠比野生型小鼠对伽马辐射更敏感。流式细胞仪分析显示，照射后处于G2/M期的细胞周期蛋白G1(-/-)MEF比细胞周期蛋白G1(+/+)MEF减少50%，提示细胞周期蛋白ct在细胞应激后的G2/M期阻滞、损伤修复和生长促进中发挥作用。
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 Ct 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 ct plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress.