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Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.
Open accessAbstract
Complementation group C of xeroderma pigmentosum (XP) represents one of the most common forms of this cancer-prone DNA repair syndrome. The primary defect is located in the subpathway of the nucleotide excision repair system, dealing with the removal of lesions from the non-transcribing sequences ('genome-overall' repair). Here we report the purification to homogeneity and subsequent cDNA cloning of a repair complex by in vitro complementation of the XP-C defect in a cell-free repair system containing UV-damaged SV40 minichromosomes. The complex has a high affinity for ssDNA and consists of two tightly associated proteins of 125 and 58 kDa. The 125 kDa subunit is an N-terminally extended version of previously reported XPCC gene product which is thought to represent the human homologue of the Saccharomyces cerevisiae repair gene RAD4. The 58 kDa species turned out to be a human homologue of yeast RAD23. Unexpectedly, a second human counterpart of RAD23 was identified. All RAD23 derivatives share a ubiquitin-like N-terminus. The nature of the XP-C defect implies that the complex exerts a unique function in the genome-overall repair pathway which is important for prevention of skin cancer.
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“hHR23B-XPC complex or only XPC exhibits a similar high affinity for both UV-induced single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) [230, 259], preferentially binds to DNA with various lesions [259] and even to small bubble structures with or without a lesion [260].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [230]
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“Both hHR23A and -B harbor a ubiquitin-like moiety at their amino terminus [230].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [230]
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Citations
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Cited by
Sorted by citations
Mechanisms of DNA damage, repair, and mutagenesis
Chatterjee, N., & Walker, G. C. (2017) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22087 · Cited by 2,039
“This complex scans for the presence of tran- sient single-stranded DNA (ssDNA) caused by disrupted base pairing due to the lesion [Masutani et al., 1994; Nishi et al., 2005].”
DNA repair pathways as targets for cancer therapy
Helleday, T., Petermann, E., Lundin, C., Hodgson, B., & Sharma, R. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2342 · Cited by 1,666
Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair
Rastogi, R. P., Richa, Kumar, A., Tyagi, M. B., & Sinha, R. P. (2010) · Journal of Nucleic Acids · doi:10.4061/2010/592980 · Cited by 1,329
“hHR23B-XPC complex or only XPC exhibits a similar high affinity for both UV-induced single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) [230, 259], preferentially binds to DNA with various lesions [259] and even to small bubble structures with or without a lesion [260].”
BackgroundThe XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
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Self-citationUnderstanding nucleotide excision repair and its roles in cancer and ageing
Marteijn, J. A., Lans, H., Vermeulen, W., & Hoeijmakers, J. H. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3822 · Cited by 1,192
Metadata
- Authors
- Masutani, C., Sugasawa, K., Yanagisawa, J., Sonoyama, T., Ui, M., Enomoto, T., Takio, K., Tanaka, K., van der Spek, P. J., & Bootsma, D.
- Affiliations
- RIKEN (JP)
- Venue
- The EMBO Journal
- Published
- 1994-04-01
- Volume
- 13
- Issue
- 8
- Pages
- 1831-1843
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC395023
- OpenAlex
- W1005028082
- Cited by
- 400
- References
- 70
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 7 · 2013: 5 · 2012: 9
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Cosmetology Research Foundation
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- xeroderma pigmentosum group C, nucleotide excision repair, Rad23, Rad4, UV-damaged DNA, single-stranded DNA binding, cDNA cloning, protein complex purification, skin cancer prevention, SV40 minichromosomes
- MeSH terms
- Amino Acid Sequence, Base Sequence, DNA Damage, DNA Repair, DNA-Binding Proteins, DNA, Viral, Fungal Proteins, HeLa Cells, Humans, Models, Molecular, Molecular Sequence Data, Transglutaminases, Simian virus 40, Ubiquitins, Ultraviolet Rays, Sequence Homology, Amino Acid, DNA, Complementary, Schizosaccharomyces pombe Proteins, DNA Repair Enzymes
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