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The intertwined roles of transcription and repair proteins
Yick W Fong1, Claudia Cattoglio, Robert Tjian
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Abstract:
Transcription is apparently risky business. Its intrinsic mutagenic potential must be kept in check by networks of DNA repair factors that monitor the transcription process to repair DNA lesions that could otherwise compromise transcriptional fidelity and genome integrity. Intriguingly, recent studies point to an even more direct function of DNA repair complexes as coactivators of transcription and the unexpected role of "scheduled" DNA damage/repair at gene promoters. Paradoxically, spontaneous DNA double-strand breaks also induce ectopic transcription that is essential for repair. Thus, transcription, DNA damage, and repair may be more physically and functionally intertwined than previously appreciated.
Insights
Transcription involves DNA repair factors to maintain genome integrity. Recent findings reveal DNA damage and repair can actively coactivate transcription, highlighting their intertwined roles.
Area of Science:
- Molecular Biology
- Genetics
- DNA Repair Mechanisms
Background:
- Transcription, the process of creating RNA from DNA, carries inherent mutagenic risks.
- DNA repair factors are crucial for maintaining transcriptional fidelity and genome integrity by fixing DNA lesions.
- Existing knowledge suggests a protective role for DNA repair during transcription.
Purpose of the Study:
- To explore the direct involvement of DNA repair complexes in transcriptional regulation.
- To investigate the role of "scheduled" DNA damage and repair at gene promoters.
- To understand the paradoxical induction of transcription by DNA double-strand breaks for repair purposes.
Main Methods:
- Review of recent studies on DNA repair complexes and transcription.
- Analysis of experimental evidence for DNA damage/repair at gene promoters.
- Examination of findings on transcription induction by DNA double-strand breaks.
Main Results:
- DNA repair complexes function directly as coactivators of transcription.
- "Scheduled" DNA damage and repair events occur at gene promoters.
- Spontaneous DNA double-strand breaks induce specific ectopic transcription essential for their own repair.
Conclusions:
- Transcription, DNA damage, and DNA repair are intricately linked physically and functionally.
- DNA repair is not solely a protective mechanism but actively participates in transcriptional processes.
- The interplay between transcription, DNA damage, and repair is more complex than previously understood.
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