Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response.
The cellular DNA damage response (DDR) is activated by many types of DNA lesions. Upon recognition of DNA damage by sensor proteins, an intricate signal transduction network is activated to coordinate diverse cellular outcomes that promote genome integrity. Key components of the DDR in mammalian cells are the checkpoint effector kinases Chk1 and Chk2 (referred to henceforth as the effector kinases; orthologous to spChk1 and spCds1 in the fission yeast S. pombe and scChk1 and scRad53 in the budding yeast S. cerevisiae). These evolutionarily conserved and structurally divergent kinases phosphorylate numerous substrates to regulate the DDR. This review will focus on recent advances in our understanding of the structure, regulation, and functions of the effector kinases in the DDR, as well as their potential roles in human disease.
Stracker
Travis H
TH
Molecular Biology, Sloan-Kettering Institute, New York, NY, USA. travis.stracker@irbbarcelona.org
Usui
Takehiko
T
Petrini
John H J
JH
D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004194:Disease; D004789:Enzyme Activation; D006801:Humans; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029702:Schizosaccharomyces pombe Proteins
D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; C578636:Cds1 protein, S pombe; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D017346:Protein Serine-Threonine Kinases