Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family

Abstract

In mammalian cells, four protein kinases form the PI3-kinase-related protein kinase (PIK) superfamily. These four enzymes-FRAP, DNA-PK, ATM, and ATR-are distinguished by their large size (all are >2500 amino acids), their common primary sequence relatedness through the carboxy-terminal protein kinase domain, and their sequence similarity to the p110 lipid kinase subunit of PI3-kinase. FRAP (FKBP12 and rapamycin-binding protein kinase) participates in mitogenic and growth factor responses in G1 and may regulate specific mRNA translation signals. DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ataxia telangiectasia and Rad 3 related) are thought to participate in responses to nuclear cues that activate DNA rearrangements or cell cycle arrests. Recent studies in this protein kinase family indicate an important role for ATM and ATR in a meiotic surveillance mechanism that may regulate proper chromosome transmission.