Phosphatases, DNA damage checkpoints and checkpoint deactivation.
Cells have evolved intricate and specialized responses to DNA damage, central to which are the DNA damage checkpoints that arrest cell cycle progression and facilitate the repair process. Activation of these damage checkpoints relies heavily on the activity of Ser/Thr kinases, such as Chk1 and Chk2 (Saccharomyces cerevisiae Rad53), which are themselves activated by phosphorylation. Only more recently have we begun to understand how cells disengage the checkpoints to reenter the cell cycle. Here, we review progress toward understanding the functions of phosphatases in checkpoint deactivation in S. cerevisiae, focusing on the non-redundant roles of the type 2A phosphatase Pph3 and the PP2C phosphatases Ptc2 and Ptc3 in the deactivation of Rad53. We discuss how these phosphatases may specifically recognize different phosphorylated forms of Rad53 and how each may independently regulate different facets of the checkpoint response. In conjunction with the independent dephosphorylation of other checkpoint proteins, such regulation may allow a more tailored response to DNA damage that is coordinated with the repair process, ultimately resulting in the resumption of growth.
Heideker
Johanna
J
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Lis
Ewa T
ET
Romesberg
Floyd E
FE
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C502440:PPH3 protein, S cerevisiae; C000607464:PTC3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C