Cellular response to genotoxic stress is a very complex process, and it usually starts with the “sensing” or “detection” of the DNA damage,followed by a series of events that include signal transduction and activa...Cellular response to genotoxic stress is a very complex process, and it usually starts with the “sensing” or “detection” of the DNA damage,followed by a series of events that include signal transduction and activation of transcription factors.The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair,cell cycle arrest,and cell death. There havebeen extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process,including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood,human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.展开更多
基金Supported by National Key Basic Research and DevelopmentProgram No.2002CB512901,ChinaNational Natural Science Foundation No.30300277,Chinathe Initial Funds for Returned Overseas Chinese Scholar from Zhejiang University and Ministry of Education,China
文摘Cellular response to genotoxic stress is a very complex process, and it usually starts with the “sensing” or “detection” of the DNA damage,followed by a series of events that include signal transduction and activation of transcription factors.The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair,cell cycle arrest,and cell death. There havebeen extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process,including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood,human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.
