Human CDC25B and CDC25C differ by their ability to restore a functional checkpoint response after gene replacement in fission yeast

Biochem Biophys Res Commun. 2002 Jul 19;295(3):673-7. doi: 10.1016/s0006-291x(02)00739-8.

Abstract

In fission yeast, inactivation of the Cdc25 phosphatase by checkpoint kinases participates in the signaling cascade that temporarily stops cell cycle progression after DNA damage. In human, CDC25B and C are also known to be targeted by a similar checkpoint machinery. We have examined by homologous recombination, whether CDC25B and CDC25C were able to substitute for the function of fission yeast Cdc25. We demonstrate that (i) CDC25B and C efficiently replace Cdc25 for vegetative growth, (ii) CDC25C is able to restore a functional checkpoint in response to ionizing radiation in both a Chk1- and Cds1-dependent manner, (iii) CDC25B and C are equally efficient in the response to UV irradiation, CDC25B being only dependent on Chk1, while CDC25C depends on both Chk1 and Cds1, and (iv) CDC25C is able to restore a functional DNA replication checkpoint induced by hydroxyurea in a Cds1-dependent manner. The consequences of these findings on our current view of the checkpoint cascade are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / physiology*
  • DNA Damage*
  • Dose-Response Relationship, Radiation
  • Fungal Proteins / genetics
  • Humans
  • Hydroxyurea / pharmacology
  • Models, Genetic
  • Plasmids / metabolism
  • Recombination, Genetic*
  • Schizosaccharomyces / genetics*
  • Ultraviolet Rays
  • cdc25 Phosphatases / genetics*
  • cdc25 Phosphatases / physiology*
  • ras-GRF1 / genetics

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • ras-GRF1
  • CDC25B protein, human
  • CDC25C protein, human
  • cdc25 Phosphatases
  • Hydroxyurea