• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

G(1)/S and G(2)/M cyclin-dependent kinase activities commit cells to death in the absence of the S-phase checkpoint.

The Mec1 and Rad53 protein kinases are essential for budding yeast cell viability and are also required to activate the S-phase checkpoint, which supports DNA replication under stress conditions. Whether these two functions are related to each other remains to be determined, and the nature of the replication stress-dependent lethality of mec1 and rad53 mutants is still unclear. We show here that a decrease in cyclin-dependent kinase 1 (Cdk1) activity alleviates the lethal effects of mec1 and rad53 mutations both in the absence and in the presence of replication stress, indicating that the execution of a certain Cdk1-mediated event(s) is detrimental in the absence of Mec1 and Rad53. This lethality involves Cdk1 functions in both G(1) and mitosis. In fact, delaying either the G(1)/S transition or spindle elongation in mec1 and rad53 mutants allows their survival both after exposure to hydroxyurea and under unperturbed conditions. Altogether, our studies indicate that inappropriate entry into S phase and segregation of incompletely replicated chromosomes contribute to cell death when the S-phase checkpoint is not functional. Moreover, these findings suggest that the essential function of Mec1 and Rad53 is not necessarily separated from the function of these kinases in supporting DNA synthesis under stress conditions.

Pubmed ID: 23045388

Authors

  • Manfrini N
  • Gobbini E
  • Baldo V
  • Trovesi C
  • Lucchini G
  • Longhese MP

Journal

Molecular and cellular biology

Publication Data

December 27, 2012

Associated Grants

None

Mesh Terms

  • CDC2 Protein Kinase
  • Cell Cycle Proteins
  • Checkpoint Kinase 2
  • DNA Replication
  • G1 Phase Cell Cycle Checkpoints
  • G2 Phase Cell Cycle Checkpoints
  • Genes, Fungal
  • Hydroxyurea
  • Intracellular Signaling Peptides and Proteins
  • Mutation
  • Protein-Serine-Threonine Kinases
  • S Phase Cell Cycle Checkpoints
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins