Never-in-mitosis related kinase 1 functions in DNA damage response and checkpoint control

Yumay Chen, Phang Lang Chen, Chi Fen Chen, Xianzhi Jiang, Daniel J. Riley

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1-/- mice fail to arrest properly at G1/S and M-phase checkpoints in response to DNA damage. G1-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1-/- murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair.

Original languageEnglish (US)
Pages (from-to)3194-3201
Number of pages8
JournalCell Cycle
Volume7
Issue number20
DOIs
StatePublished - Oct 15 2008

Keywords

  • Checkpoint control
  • Chromosome breaks
  • Mitosis
  • Radiation
  • S-phase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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