RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6.
Open accessAbstract
Transcription-coupled repair (TCR) is a universal sub-pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes. It accomplishes the preferential elimination of transcription-blocking DNA lesions and permits rapid resumption of the vital process of transcription. A defect in TCR is responsible for the rare hereditary disorder Cockayne syndrome (CS). Recently we found that mutations in the ERCC6 repair gene, encoding a putative helicase, underly the repair defect of CS complementation group B. Here we report the cloning and characterization of the Saccharomyces cerevisiae homolog of CSB/ERCC6, which we designate RAD26. A rad26 disruption mutant appears viable and grows normally, indicating that the gene does not have an essential function. In analogy with CS, preferential repair of UV-induced cyclobutane pyrimidine dimers in the transcribed strand of the active RBP2 gene is severely impaired. Surprisingly, in contrast to the human CS mutant, yeast RAD26 disruption does not induce any UV-, cisPt- or X-ray sensitivity, explaining why it was not isolated as a mutant before. Recovery of growth after UV exposure was somewhat delayed in rad26. These findings suggest that TCR in lower eukaryotes is not very important for cell survival and that the global genome repair pathway of NER is the major determinant of cellular resistance to genotoxicity.
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- Authors
- van Gool, A. J., Verhage, R., Swagemakers, S. M., van de Putte, P., Brouwer, J., Troelstra, C., Bootsma, D., & Hoeijmakers, J. H.
- Affiliations
- Erasmus University Rotterdam (NL)
- ORCID
- Hoeijmakers, J.H.
- Venue
- The EMBO Journal
- Published
- 1994-11-01
- Volume
- 13
- Issue
- 22
- Pages
- 5361-5369
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC395493
- OpenAlex
- W2112652171
- Cited by
- 246
- References
- 56
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 3 · 2014: 7 · 2013: 7 · 2012: 4
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- Rad26, ERCC6, Cockayne syndrome B, transcription-coupled repair, nucleotide excision repair, Saccharomyces cerevisiae, cyclobutane pyrimidine dimers, UV-induced DNA damage, RBP2, global genome repair, cisplatin sensitivity, X-ray sensitivity, helicase, gene essentiality
- MeSH terms
- Poly-ADP-Ribose Binding Proteins, Amino Acid Sequence, Cockayne Syndrome, DNA Damage, DNA Repair, DNA Helicases, DNA, Fungal, Fungal Proteins, Genes, Fungal, Humans, Molecular Sequence Data, Saccharomyces cerevisiae, Species Specificity, Transcription, Genetic, Ultraviolet Rays, Sequence Alignment, Sequence Homology, Amino Acid, Cell Cycle Proteins, Schizosaccharomyces pombe Proteins, DNA Repair Enzymes
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