Recapitulation of the cellular xeroderma pigmentosum-variant phenotypes using short interfering RNA for DNA polymerase H

Cancer Res. 2003 Jul 15;63(14):3909-12.


The lesion-specific DNA polymerase POLH gene is mutated in xeroderma pigmentosum variant (XP-V) patients who exhibit an increased skin cancer incidence from UV exposure. Normal cells in which POLH expression was reduced using short interfering RNAs (siRNAs) were compared with the XP-V cellular phenotype that results from naturally occurring inactivating mutations. Stable clones expressing siRNA had partially reduced POLH protein levels, and intermediate levels of UV sensitivity and S phase checkpoint activation, but similar levels of Mre11 foci as in XP-V cells. Therefore, suppression of POLH expression levels by siRNA recapitulates most of the phenotypes seen in cells from XP-V patients with inactivating mutations in POLH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Caffeine / pharmacology
  • Cell Line, Transformed
  • DNA-Directed DNA Polymerase / genetics
  • Endodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / genetics
  • Fibroblasts / enzymology
  • Fibroblasts / physiology
  • Fibroblasts / radiation effects
  • Humans
  • Nucleic Acid Synthesis Inhibitors*
  • Plasmids / genetics
  • RNA, Small Interfering / genetics*
  • S Phase / genetics
  • S Phase / radiation effects
  • Saccharomyces cerevisiae Proteins / genetics
  • Transfection
  • Ultraviolet Rays / adverse effects
  • Xeroderma Pigmentosum / enzymology*
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum / prevention & control


  • Nucleic Acid Synthesis Inhibitors
  • RNA, Small Interfering
  • Saccharomyces cerevisiae Proteins
  • Caffeine
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae