A unified view of the DNA-damage checkpoint.
Recent investigation of the DNA-damage checkpoint in several organisms has highlighted the conservation of this pathway. The checkpoint's signal transduction pathway consists of four conserved classes of molecules: two large protein kinases having homology to phosphatidylinositol 3-kinases, three "sensor" proteins with homology to proliferating cell nuclear antigen, two serine/threonine (S/T) kinases, and two adaptors for the S/T kinases. This review compares the role of these four classes of checkpoint proteins in humans and model organisms.
Melo
Justine
J
Department of Biochemistry and Biophysics, Mount Zion Cancer Research Center, University of California, San Francisco, CA 94115, USA. jmelo@itsa.ucsf.edu
Toczyski
David
D
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction / Q000502:physiology*; D029867:Xenopus Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D019869:Phosphatidylinositol 3-Kinases; D018809:Proliferating Cell Nuclear Antigen; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D029867:Xenopus Proteins; C416368:CLSPN protein, Xenopus; C488158:CLSPN protein, human; C106332:hus1 protein, S pombe; C069930:rad9 protein; C578634:CHEK2 protein, human; C578636:Cds1 protein, S pombe; C069266:RAD1 protein, S cerevisiae