Cited by 242DNA Repair MechanismsNuclear Structure and FunctionCarcinogens and Genotoxicity Assessment

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Transcription‐coupled repair removes both cyclobutane pyrimidine dimers and 6‐4 photoproducts with equal efficiency and in a sequential way from transcribed DNA in xeroderma pigmentosum group C fibroblasts.

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van Hoffen, A., Venema, J., Meschini, R., van Zeeland, A.A., Mullenders, L.H.·1995·The EMBO Journal

DOI 10.1002/j.1460-2075.1995.tb07010.xPMC PMC398090

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Abstract

We investigated the contribution of the global and the transcription-coupled nucleotide excision repair pathway to the removal of structurally different DNA lesions. The repair kinetics of UV-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) were determined in an active and inactive gene in normal human fibroblasts and in xeroderma pigmentosum group C (XP-C) fibroblasts. Previously we have shown that in normal human cells exposed to a UV dose of 10 J/m2 repair of CPDs takes place via two pathways: global repair and transcription-coupled repair, the latter being responsible for accelerated repair of CPDs in the transcribed strand of active genes. So far, no clear evidence for transcription-coupled repair of 6-4PPs has been presented. Here we demonstrate that 6-4PPs really form a target for transcription-coupled repair. In XP-C cells, exposed to 30 J/m2 and only capable of performing transcription-coupled repair, CPDs as well as 6-4PPs are removed selectively and with similar kinetics from the transcribed strand of the adenosine deaminase (ADA) gene. The non-transcribed strand of the ADA gene and the inactive 754 gene are hardly repaired. In contrast to XP-C cells, normal cells exposed to 30 J/m2 lack strand-specific repair of both 6-4PPs and CPDs, suggesting that transcription-coupled repair is overruled by global repair, probably due to severe inhibition of transcription at this high UV dose. The much more rapid repair of 6-4PPs compared with CPDs in normal cells may be related to higher affinity of the global repair system for the former lesion. In XP-C cells the similarity of the rate of repair of both 6-4PPs and CPDs in the transcribed strand at 30 J/m2 indicates that transcription-coupled repair of photolesions takes place in a sequential way. Our results strongly suggest that the significance of transcription-coupled repair for removal of lesions depends on the type of lesion and on the dose employed.

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Authors: van Hoffen, A., Venema, J., Meschini, R., van Zeeland, A. A., & Mullenders, L. H.
Affiliations: Leiden University (NL)
ORCID: Meschini, R.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1995-01-01
Volume: 14
Issue: 2
Pages: 360-367
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1995.tb07010.x
PMC: PMC398090
OpenAlex: W1889725400
Cited by: 242
References: 38
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 6
FWCI: 6.69
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Universiteit Leiden
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 › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: transcription-coupled repair, cyclobutane pyrimidine dimers, 6-4 photoproducts, xeroderma pigmentosum group C, UV-induced DNA damage, repair kinetics, strand-specific repair, UV dose dependence
MeSH terms: Cells, Cultured, DNA, DNA Repair, Endodeoxyribonucleases, Fibroblasts, Humans, Photochemistry, Pyrimidine Dimers, Transcription, Genetic, Ultraviolet Rays, Xeroderma Pigmentosum, Escherichia coli Proteins

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Transcription‐coupled repair removes both cyclobutane pyrimidine dimers and 6‐4 photoproducts with equal efficiency and in a sequential way from transcribed DNA in xeroderma pigmentosum group C fibroblasts.

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