Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation

Cell Cycle. 2008 Sep 1;7(17):2705-9. doi: 10.4161/cc.7.17.6551. Epub 2008 Sep 3.

Abstract

Nek6 is a recently identified NIMA-related kinase that is required for mitotic cell cycle progression. In the present study, we examined the role of Nek6 in the DNA damage response. We found that Nek6 is phosphorylated upon IR and UV irradiation through the DNA damage checkpoint in vivo. Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro. Notably, Nek6 activation during mitosis is completely abolished by IR and UV irradiation. Moreover, the ectopic expression of Nek6 overrides DNA damage-induced G(2)/M arrest. These results suggest that Nek6 is a novel target of the DNA damage checkpoint and that the inhibition of Nek6 activity is required for proper cell cycle arrest in the G(2)/M phase upon DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division*
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • DNA Damage*
  • Enzyme Activation
  • G2 Phase*
  • HeLa Cells
  • Humans
  • NIMA-Related Kinases
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Substrate Specificity

Substances

  • Protein Kinases
  • Checkpoint Kinase 2
  • CHEK1 protein, human
  • CHEK2 protein, human
  • Checkpoint Kinase 1
  • NIMA-Related Kinases
  • NIMA-related kinase 6
  • Protein-Serine-Threonine Kinases