A Rad26-Def1 complex coordinates repair and RNA pol II proteolysis in response to DNA damage

Nature. 2002 Feb 21;415(6874):929-33. doi: 10.1038/415929a.

Abstract

Eukaryotic cells use multiple, highly conserved mechanisms to contend with ultraviolet-light-induced DNA damage. One important response mechanism is transcription-coupled repair (TCR), during which DNA lesions in the transcribed strand of an active gene are repaired much faster than in the genome overall. In mammalian cells, defective TCR gives rise to the severe human disorder Cockayne's syndrome (CS). The best-studied CS gene, CSB, codes for a Swi/Snf-like DNA-dependent ATPase, whose yeast homologue is called Rad26 (ref. 4). Here we identify a yeast protein, termed Def1, which forms a complex with Rad26 in chromatin. The phenotypes of cells lacking DEF1 are consistent with a role for this factor in the DNA damage response, but Def1 is not required for TCR. Rather, def1 cells are compromised for transcript elongation, and are unable to degrade RNA polymerase II (RNAPII) in response to DNA damage. Our data suggest that RNAPII stalled at a DNA lesion triggers a coordinated rescue mechanism that requires the Rad26-Def1 complex, and that Def1 enables ubiquitination and proteolysis of RNAPII when the lesion cannot be rapidly removed by Rad26-promoted DNA repair.

Publication types

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

MeSH terms

  • Cell Cycle Proteins*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / isolation & purification
  • Chromosomal Proteins, Non-Histone / physiology*
  • DNA Damage
  • DNA Repair*
  • DNA, Fungal / radiation effects
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Genes, Fungal
  • Macromolecular Substances
  • RNA Polymerase II / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / physiology*
  • Schizosaccharomyces pombe Proteins*
  • Transcription, Genetic
  • Ubiquitin / metabolism
  • Ultraviolet Rays
  • Yeasts / enzymology
  • Yeasts / genetics
  • Yeasts / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DEF1 protein, S cerevisiae
  • DNA, Fungal
  • Fungal Proteins
  • Macromolecular Substances
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Ubiquitin
  • rad26 protein, S pombe
  • RNA Polymerase II

Associated data

  • PDB/1JPL
  • PDB/1JUQ