DOI: 10.1073/pnas.170280397. A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage

A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage

10.1073/pnas.170280397

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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.

Bibliography

VispÃ©, S., Yung, T. M. C., Ritchot, J., Serizawa, H., & Satoh, M. S. (2000). A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage. Proceedings of the National Academy of Sciences, 97(18), 9886â9891.

Authors 5

Stéphane Vispé (first)
Tetsu M. C. Yung (additional)
Janelle Ritchot (additional)
Hiroaki Serizawa (additional)
Masahiko S. Satoh (additional)

References 42 Referenced 67

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 6:31 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 10:07 p.m.)
Indexed	2 months, 3 weeks ago (June 10, 2025, 3:04 p.m.)
Issued	25 years ago (Aug. 15, 2000)
Published	25 years ago (Aug. 15, 2000)
Published Online	25 years ago (Aug. 15, 2000)
Published Print	25 years ago (Aug. 29, 2000)

Funders 0

None

BibTeX

@article{Visp__2000, title={A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.170280397}, DOI={10.1073/pnas.170280397}, number={18}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Vispé, Stéphane and Yung, Tetsu M. C. and Ritchot, Janelle and Serizawa, Hiroaki and Satoh, Masahiko S.}, year={2000}, month=aug, pages={9886–9891} }

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