title: ATM and ATR: sensing DNA damage.
abstract: 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.
authors.affiliation: Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, 353 Yanan Road, Hangzhou, 310031, Zhejiang Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Xu
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Hope E
authors.initials: HE
authors.lastname: Hamrick
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Duerksen-Hughes
authors.forename: Ying-Nian
authors.initials: YN
authors.lastname: Yu
mesh_terms: 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
chemical_list: D018797:Cell Cycle Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases