v-Src inhibits the interaction between Rad17 and Rad9 and induces replication fork collapse

Biochem Biophys Res Commun. 2014 Jul 18;450(1):885-90. doi: 10.1016/j.bbrc.2014.06.078. Epub 2014 Jun 24.

Abstract

ATR-dependent DNA damage checkpoint is crucial to maintain genomic stability. Recently, we showed that Src family kinases suppress ATR-dependent checkpoint signaling in termination of DNA damage checkpoint. However, the precise molecular mechanism is unclear. Therefore, we examined the role of oncogenic v-Src on ATR-Chk1 signaling. We show that v-Src suppresses thymidine-induced Chk1 phosphorylation and induces replication fork collapse. v-Src inhibits interaction between Rad17 and Rad9 in chromatin fraction. By contrast, v-Src does not inhibit RPA32 phosphorylation, ATR autophosphorylation, or TopBP1-Rad9 interaction. These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.

Keywords: ATR; DNA damage checkpoint; Rad17; Rad9; v-Src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Checkpoints / physiology*
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 1
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • DNA Replication / physiology*
  • HeLa Cells
  • Humans
  • Oncogene Protein pp60(v-src) / metabolism*
  • Protein Binding
  • Protein Kinases / metabolism
  • Signal Transduction / physiology

Substances

  • Cell Cycle Proteins
  • Rad17 protein, human
  • rad9 protein
  • Protein Kinases
  • Oncogene Protein pp60(v-src)
  • CHEK1 protein, human
  • Checkpoint Kinase 1