Open AccessA cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage
Author(s) -
Stéphane Vispé,
Tetsu M.C. Yung,
Janelle Ritchot,
Hiroaki Serizawa,
Masahiko S. Satoh
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.170280397
Subject(s) - poly adp ribose polymerase , polymerase , transcription (linguistics) , dna damage , rna polymerase ii , biology , microbiology and biotechnology , dna repair , rna polymerase i , dna , rna polymerase , biochemistry , rna , rna dependent rna polymerase , gene expression , gene , promoter , linguistics , philosophy
DNA damage is known to trigger key cellular defense pathways such as those involved in DNA repair. Here we provide evidence for a previously unrecognized pathway regulating transcription in response to DNA damage and show that this regulation is mediated by the abundant nuclear enzyme poly(ADP-ribose) polymerase. We found that poly(ADP-ribose) polymerase reduced the rate of transcription elongation by RNA polymerase II, suggesting that poly(ADP-ribose) polymerase negatively regulates transcription, possibly through the formation of poly(ADP-ribose) polymerase–RNA complexes. In damaged cells, poly(ADP-ribose) polymerase binds to DNA breaks and automodifies itself in the presence of NAD+ , resulting in poly(ADP-ribose) polymerase inactivation. We found that automodification of poly(ADP-ribose) polymerase in response to DNA damage resulted in the up-regulation of transcription, presumably because automodified poly(ADP-ribose) polymerase molecules were released from transcripts, thereby relieving the block on transcription. Because agents that damage DNA damage RNA as well, up-regulation of RNA synthesis in response to DNA damage may provide cells with a mechanism to compensate for the loss of damaged transcripts and may be critical for cell survival after exposure to DNA-damaging agents.