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Review:DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis 被引量:18
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作者 SCHMITT Estelle PAQUET Claudie +1 位作者 BEAUCHEMIN Myriam BERTRAND Richard 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2007年第6期377-397,共21页
Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase ... Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senes- cence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving “sensor” proteins that sense the damage, and transmit signals to “transducer” proteins, which, in turn, convey the signals to numerous “effector” proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation. 展开更多
关键词 dna-damage response network Cell cycle Cellular senescence APOPTOSIS Bcl-2 family
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基于重组发光酵母的遗传毒性检测技术及应用
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作者 杨倩 朱茜 +4 位作者 李方旭 桂萍 张瑞娜 刘春 周小红 《环境科学学报》 CAS CSCD 北大核心 2023年第8期464-472,共9页
基于酵母DNA损伤响应网络,本研究选择4种生物标志物,以丝裂霉素C(MMC)为模型遗传毒物,双酚A为阴性对照,通过优化实验条件,建立了一种基于重组发光酵母的遗传毒性检测技术.结果表明:菌液培养体积为60μL、微板阅读器增益设置为100是最佳... 基于酵母DNA损伤响应网络,本研究选择4种生物标志物,以丝裂霉素C(MMC)为模型遗传毒物,双酚A为阴性对照,通过优化实验条件,建立了一种基于重组发光酵母的遗传毒性检测技术.结果表明:菌液培养体积为60μL、微板阅读器增益设置为100是最佳的检测条件;并在此条件下,将MMC暴露在酵母中,其毒性特征谱图在2 h分析长度内呈现出明显的浓度与时间依赖性,从剂量-响应曲线上得出其遗传毒性作用的最低浓度为0.04 mg·L^(-1);阴性对照双酚A的实时蛋白表达图谱则与MMC完全相反,并未呈现出浓度与时间的依赖关系.将上述方法应用于中国北方黄河中下游某村镇地表水及可疑污染源水样的遗传毒性测试,结果表明:当浓缩倍数为100倍时,14个测试点位中有6个点位处的水样被检出阳性;当浓缩倍数为10倍时,水样均呈阴性. 展开更多
关键词 遗传毒性 重组发光酵母 dna损伤响应网络 地表水
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