Novel evidences for a tumor suppressor role of Rev3, the catalytic subunit of Pol zeta

Oncogene. 2008 Oct 16;27(47):6093-101. doi: 10.1038/onc.2008.212. Epub 2008 Jul 14.


Cell cycle checkpoints and DNA repair act in concert to ensure DNA integrity during perturbation of normal replication or in response to genotoxic agents. Deficiencies in these protective mechanisms can lead to cellular transformation and ultimately tumorigenesis. Here we focused on Rev3, the catalytic subunit of the low-fidelity DNA repair polymerase zeta. Rev3 is believed to play a role in double-strand break (DSB)-induced DNA repair by homologous recombination. In line with this hypothesis, we show the accumulation of chromatin-bound Rev3 protein in late S-G2 of untreated cells and in response to clastogenic DNA damage as well as an gamma-H2AX accumulation in Rev3-depleted cells. Moreover, serine 995 of Rev3 is in vitro phosphorylated by the DSB-inducible checkpoint kinase, Chk2. Our data also disclose a significant reduction of rev3 gene expression in 74 colon carcinomas when compared to the normal adjacent tissues. This reduced expression is independent of the carcinoma stages, suggesting that the downregulation of rev3 might have occurred early during tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cells, Cultured
  • Checkpoint Kinase 2
  • Colonic Neoplasms / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA Replication
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • DNA-Directed DNA Polymerase / analysis
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / physiology*
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Phosphorylation
  • Protein Serine-Threonine Kinases / physiology
  • RNA, Messenger / analysis
  • S Phase
  • Tumor Suppressor Proteins / physiology*


  • DNA-Binding Proteins
  • H2AX protein, human
  • Histones
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases
  • DNA polymerase zeta
  • DNA-Directed DNA Polymerase
  • REV3L protein, human