PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break.
Saccharomyces cells suffering a DNA double-strand break (DSB) ultimately escape checkpoint-mediated G2/M arrest either by recovery once the lesion is repaired or by adaptation if the lesion proves irreparable. Cells lacking the PP2C-like phosphatases Ptc2 and Ptc3 are unable to adapt to a HO-induced DSB and are also defective in recovering from a repairable DSB. In contrast, overexpression of PTC2 rescues adaptation-defective yku80Delta and cdc5-ad mutants. These effects are not explained by alterations either in the processing of DSB ends or in DSB repair. In vivo and in vitro evidence suggests that phosphorylated forms of Ptc2 and Ptc3 specifically bind to the Rad53 FHA1 domain and inactivate Rad53-dependent pathways during adaptation and recovery by dephosphorylating Rad53.
Leroy
Christophe
C
Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, 91191 Gif-sur-Yvette, Cedex, France.
Lee
Sang Eun
SE
Vaze
Moreshwar B
MB
Ochsenbein
Françoise
F
Ochsenbien
Françoise
F
Guerois
Raphaël
R
Haber
James E
JE
Marsolier-Kergoat
Marie-Claude
MC
D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D016195:G2 Phase; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008938:Mitosis; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D004247:DNA; D005982:Glutathione Transferase; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; C491716:PTC2 protein, S cerevisiae; C000607464:PTC3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D010744:Phosphoric Monoester Hydrolases