ATM and ATR: sensing DNA damage.
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 have been 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.
Yang
Jun
J
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, 353 Yanan Road, Hangzhou, 310031, Zhejiang Province, China.
Xu
Zheng-Ping
ZP
Huang
Yun
Y
Hamrick
Hope E
HE
Duerksen-Hughes
Penelope J
PJ
Yu
Ying-Nian
YN
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases
D018797:Cell Cycle Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases