PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break

Mol Cell. 2003 Mar;11(3):827-35. doi: 10.1016/s1097-2765(03)00058-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2
  • DNA / metabolism*
  • DNA Damage*
  • G2 Phase
  • Glutathione Transferase / metabolism
  • Kinetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mitosis
  • Mutation
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / physiology*
  • Phosphoric Monoester Hydrolases*
  • Phosphorylation
  • Plasmids / metabolism
  • Protein Phosphatase 2
  • Protein Phosphatase 2C
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Time Factors

Substances

  • Cell Cycle Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • rad9 protein
  • DNA
  • Glutathione Transferase
  • Checkpoint Kinase 2
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae
  • PTC2 protein, S cerevisiae
  • PTC3 protein, S cerevisiae
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Protein Phosphatase 2C
  • Phosphoric Monoester Hydrolases