• 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

The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint.

In response to DNA damage in G2, mammalian cells must avoid entry into mitosis and instead initiate DNA repair. Here, we show that, in response to genotoxic stress in G2, the phosphatase Cdc14B translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase APC/C(Cdh1), with the consequent degradation of Plk1, a prominent mitotic kinase. This process induces the stabilization of Claspin, an activator of the DNA-damage checkpoint, and Wee1, an inhibitor of cell-cycle progression, and allows an efficient G2 checkpoint. As a by-product of APC/C(Cdh1) reactivation in DNA-damaged G2 cells, Claspin, which we show to be an APC/C(Cdh1) substrate in G1, is targeted for degradation. However, this process is counteracted by the deubiquitylating enzyme Usp28 to permit Claspin-mediated activation of Chk1 in response to DNA damage. These findings define a novel pathway that is crucial for the G2 DNA-damage-response checkpoint.

Pubmed ID: 18662541

Authors

  • Bassermann F
  • Frescas D
  • Guardavaccaro D
  • Busino L
  • Peschiaroli A
  • Pagano M

Journal

Cell

Publication Data

July 25, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM057587
  • Agency: NIGMS NIH HHS, Id: R01 GM057587-09
  • Agency: NIGMS NIH HHS, Id: R01 GM057587-09S1
  • Agency: NIGMS NIH HHS, Id: R01 GM057587-10
  • Agency: NIGMS NIH HHS, Id: R01 GM057587-11
  • Agency: NCI NIH HHS, Id: R21 CA125173
  • Agency: NCI NIH HHS, Id: R21 CA125173-01
  • Agency: NCI NIH HHS, Id: R21 CA125173-02
  • Agency: NCI NIH HHS, Id: R37 CA076584
  • Agency: NCI NIH HHS, Id: R37 CA076584-09
  • Agency: NCI NIH HHS, Id: R37 CA076584-10
  • Agency: NCI NIH HHS, Id: R37 CA076584-11
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Anaphase-Promoting Complex-Cyclosome
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Nucleus
  • DNA Damage
  • DNA Repair
  • Dual-Specificity Phosphatases
  • G2 Phase
  • Humans
  • Mitosis
  • Neoplasms
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Signal Transduction
  • Ubiquitin Thiolesterase
  • Ubiquitin-Protein Ligase Complexes