Cited by 487DNA Repair MechanismsNuclear Structure and FunctionGenomics and Chromatin Dynamics

Transcription-coupled nucleotide excision repair in mammalian cells: Molecular mechanisms and biological effects

Fousteri, Maria, Mullenders, Leon HF·2008·Cell Research

Abstract

The encounter of elongating RNA polymerase II (RNAPIIo) with DNA lesions has severe consequences for the cell as this event provides a strong signal for P53-dependent apoptosis and cell cycle arrest. To counteract prolonged blockage of transcription, the cell removes the RNAPIIo-blocking DNA lesions by transcription-coupled repair (TC-NER), a specialized subpathway of nucleotide excision repair (NER). Exposure of mice to UVB light or chemicals has elucidated that TC-NER is a critical survival pathway protecting against acute toxic and long-term effects (cancer) of genotoxic exposure. Deficiency in TC-NER is associated with mutations in the CSA and CSB genes giving rise to the rare human disorder Cockayne syndrome (CS). Recent data suggest that CSA and CSB play differential roles in mammalian TC-NER: CSB as a repair coupling factor to attract NER proteins, chromatin remodellers and the CSA- E3-ubiquitin ligase complex to the stalled RNAPIIo. CSA is dispensable for attraction of NER proteins, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGN1 and TFIIS. The emerging picture of TC-NER is complex: repair of transcription-blocking lesions occurs without displacement of the DNA damage-stalled RNAPIIo, and requires at least two essential assembly factors (CSA and CSB), the core NER factors (except for XPC-RAD23B), and TC-NER specific factors. These and yet unidentified proteins will accomplish not only efficient repair of transcription-blocking lesions, but are also likely to contribute to DNA damage signalling events.

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Crossref · 10.1038/cr.2008.6

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96 of 96 references verified0 citation errors · 0 not checkable

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  • DNA repair machinery could selectively protect genic regions from accessible chromatin-coupled genome susceptibility, regardless of whether the gene is highly expressed or not.

    “Thus, DNA repair machinery could selectively protect genic regions from the accessible chromatin-coupled genome susceptibility, regardless of whether the gene is highly expressed or not17,48.”
  • HMGN1 interacts with RNAPII in a CSA/CSB dependent manner and works as a nucleosome binding protein that competes with histone H1 for binding with chromatin in linker regions.

    “HMGN1 also interacts with RNAPII in a CSA/CSB dependent manner and works as a nucleosome binding protein that competes with histone H1 for binding with chromatin in linker regions [99].”
  • Binding of CSA-CSB complexes leads to reverse translocation of RNA polymerase from damage sites and exposes damage for repair proteins including XAB2, USP7, and HMGN1.

    “Binding of CSA-CSB complexes leads to reverse translocation of RNA polymerase from the damage sites and expose the damage for repair proteins including XPA-binding protein 2 (XAB2), ubiquitin-specific-processing protease 7 (USP7) and high mobility group nucleosome-binding domain-containing protein 1 (HMGN1) [99].”

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Authors
Fousteri, M., & Mullenders, L. H.
Affiliations
Leiden University Medical Center (NL)
Corresponding author
Mullenders, Leon HF
Venue
Cell Research
Published
2008-01
Volume
18
Issue
1
Pages
73-84
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
OpenAlex
W2015725762
Cited by
487
References
96
Citations by year
2026: 25 · 2025: 16 · 2024: 11 · 2023: 16 · 2022: 27 · 2021: 23 · 2020: 23 · 2019: 20 · 2018: 21 · 2017: 21 · 2016: 29 · 2015: 34 · 2014: 26 · 2013: 35 · 2012: 35
FWCI
3.22
Type
journal article
Language
en
Open access
closed
Locations
  • Cell Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
ZonMw (917-46-364)
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
transcription-coupled repair, RNA polymerase II, DNA damage, CSA, CSB, Cockayne syndrome, HMGN1, TFIIS, DNA damage signaling, UVB exposure, genotoxicity, chromatin remodeling, ubiquitination
MeSH terms
Poly-ADP-Ribose Binding Proteins, Animals, Cell Survival, DNA Repair, DNA Helicases, Eukaryotic Cells, Humans, Mammals, Models, Biological, Transcription Factors, Transcription, Genetic, Signal Transduction, Mutagenesis, DNA Repair Enzymes

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