The role of ATM and ATR in DNA damage-induced cell cycle control.
Ataxia-Telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are members of the phosphatidyl inositol 3-kinase-like family of serine/threonine protein kinases (PIKKs), and play important roles in the cellular response to DNA damage. Activation of ATM by ionizing radiation results in the activation of signal transduction pathways that induce cell cycle arrest at G1/S, S and G2/M. ATR is required for cell cycle arrest in response to DNA-damaging agents such as ultraviolet radiation that cause bulky lesions. This review focuses on the role of ATM and ATR in various DNA damage response pathways, and discusses the potential for targeting these pathways for the development of novel therapeutics.
Goodarzi
Aaron A
AA
Departments of Biochemistry & Molecular Biology and Biological Sciences, University of Calgary, 2500 University Drive, N.W., Calgary, AB T2N 1N4, Canada.
Block
Wesley D
WD
Lees-Miller
Susan P
SP
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases