DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism

FEBS Lett. 2012 Nov 16;586(22):3974-9. doi: 10.1016/j.febslet.2012.09.048. Epub 2012 Oct 12.

Abstract

CHK1 regulates the DNA damage-induced checkpoint involving an ATR- or ATM- dependent pathway. In this paper, we focused on the autophosphorylation of Ser296, one of the DNA damage-induced phosphorylation sites. First, we demonstrated that the Ser296 autophosphorylation of CHK1 is mainly regulated by an intramolecular mechanism in response to DNA damage. In examining the relationship between Ser296 and Ser317/Ser345, the other ATR dependent phosphorylation sites, we found that the Ser296 cis-autophosphorylation was dependent on both Ser317 and Ser345 phosphorylation. Our findings suggest that CHK1 mediates cell cycle checkpoint signals by both cis-autophosphorylation and trans-phosphorylation of downstream factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Blotting, Western
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Checkpoint Kinase 1
  • DNA Damage*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Interference
  • Serine / genetics
  • Serine / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Serine
  • Protein Kinases
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases