The DOI matches its Crossref record; 227 of the 228 references it cites were found in a registry or an index.
The DNA damage response to transcription stress
Abstract
The spatiotemporal control of RNA polymerase II (Pol II)-mediated gene transcription is tightly and intricately regulated. In addition, preservation of the integrity of the DNA template is required so as to ensure unperturbed transcription, particularly since DNA is continually challenged by different types of damaging agents that can form transcription-blocking DNA lesions (TBLs), which impede transcription elongation and cause transcription stress. To overcome the highly cytotoxic effects of TBLs, an intricate cellular response has evolved, in which the transcription-coupled nucleotide excision repair (TC-NER) pathway has a central role in removing TBLs specifically from the transcribed strand. Damage detection by stalling of the transcribing Pol II is highly efficient, but a stalled Pol II complex may create an even bigger problem by interfering with repair of the lesions, and overall with transcription and replication. In this Review, we discuss the effects of different types of DNA damage on Pol II, important concepts of transcription stress, the manner in which TBLs are removed by TC-NER and how different tissues respond to TBLs. We also discuss the role of TBLs in ageing and the complex genotype-phenotype correlations of TC-NER hereditary disorders.
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“Moreover, consistent with the function of RNA polymerases as sensors of DNA damage-induced lesions45, inhibition of RNA polymerase subunits, such as POLR1D, POLR2B, and BRF2, may block sensing of DNA damage, resulting in cisplatin hypersensitivity.”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [45]
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Self-citation
Metadata
- Authors
- Lans, H., Hoeijmakers, J. H. J., Vermeulen, W., & Marteijn, J. A.
- Affiliations
- Erasmus MC (NL)
- University of Cologne (DE)
- Corresponding author
- Vermeulen, Wim
- Marteijn, Jurgen A.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2019-09-26
- Volume
- 20
- Issue
- 12
- Pages
- 766-784
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2977176731
- Cited by
- 321
- References
- 228
- Citations by year
- 2026: 27 · 2025: 40 · 2024: 66 · 2023: 43 · 2022: 60 · 2021: 50 · 2020: 32 · 2019: 3
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.C.182.025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RNA polymerase II, transcription-coupled repair, DNA damage response, transcription elongation, DNA repair, aging, genetic disorders, genotype-phenotype correlation
- MeSH terms
- Animals, DNA Damage, DNA Repair, DNA Replication, Humans, RNA Polymerase II, Transcription, Genetic, Genetic Diseases, Inborn
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