Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells

Cell Death Differ. 2002 Oct;9(10):1099-107. doi: 10.1038/sj.cdd.4401072.

Abstract

Cyclobutane pyrimidine dimers (CPDs) are directly involved in signaling for UV-induced apoptosis in mammalian cells. Failure to remove these lesions, specially those located at actively expressing genes, is critical, as cells defective in transcription coupled repair have increased apoptotic levels. Thus, the blockage of RNA synthesis by lesions is an important candidate event triggering off active cell death. In this work, wild-type and XPB mutated Chinese hamster ovary (CHO) cells expressing a marsupial photolyase, that removes specifically CPDs from the damaged DNA, were generated, in order to investigate the importance of this lesion in both RNA transcription blockage and apoptotic induction. Photorepair strongly recovers RNA synthesis in wild-type CHO cell line, although the resumption of transcription is decreased in XPB deficient cells. This recovery is accompanied by the prevention of cells entering into apoptosis. These results demonstrate that marsupial photolyase has access to CPDs blocking RNA synthesis in vivo, and this may be affected by the presence of a mutated XPB protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis / radiation effects
  • CHO Cells
  • Cricetinae
  • DNA Helicases
  • DNA Repair / physiology*
  • DNA Repair / radiation effects
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • DNA-Directed RNA Polymerases / metabolism*
  • DNA-Directed RNA Polymerases / radiation effects
  • Deoxyribodipyrimidine Photo-Lyase / genetics
  • Dose-Response Relationship, Radiation
  • Eukaryotic Cells / enzymology*
  • Eukaryotic Cells / radiation effects
  • Mutation / genetics
  • Pyrimidine Dimers / antagonists & inhibitors
  • Pyrimidine Dimers / metabolism*
  • RNA / biosynthesis*
  • RNA / genetics
  • Ultraviolet Rays

Substances

  • DNA-Binding Proteins
  • Pyrimidine Dimers
  • XPBC-ERCC-3 protein
  • RNA
  • DNA-Directed RNA Polymerases
  • DNA Helicases
  • Deoxyribodipyrimidine Photo-Lyase