A Rad26-Def1 complex coordinates repair and RNA pol II proteolysis in response to DNA damage.
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.
Woudstra
Elies C
EC
Mechanisms of Gene Transcription Laboratory, Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
Gilbert
Chris
C
Fellows
Jane
J
Jansen
Lars
L
Brouwer
Jaap
J
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Svejstrup
Jesper Q
JQ
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000528:radiation effects; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal; D046911:Macromolecular Substances; D012319:RNA Polymerase II / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D014466:Ultraviolet Rays; D015003:Yeasts / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C451742:DEF1 protein, S cerevisiae; D004271:DNA, Fungal; D005656:Fungal Proteins; D046911:Macromolecular Substances; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C088086:rad26 protein, S pombe; D012319:RNA Polymerase II