Substrate specificity of ultraviolet DNA endonuclease (UVDE/Uve1p) from Schizosaccharomyces pombe
Open accessAbstract
Schizosaccharomyces pombe ultraviolet DNA endonuclease (UVDE or Uve1p) has been shown to cleave 5' to UV light-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). This endonuclease is believed to function in the initial step in an alternative excision repair pathway for the removal of DNA damage caused by exposure to UV light. An active truncated form of this protein, Delta228-Uve1p, has been successfully overexpressed, affinity purified and partially characterized. In the present study we present data from a detailed substrate specificity trial. We have determined that the substrate range of Uve1p is much greater than was originally believed. We demonstrate that this DNA damage repair protein is capable of recognizing an array of UV-induced DNA photoproducts (cis-syn-, trans-syn I- and trans-syn II CPDs, 6-4PP and Dewar isomers) that cause varying degrees of distortion in a duplex DNA molecule. We also demonstrate that Uve1p recognizes non-UV-induced DNA damage, such as platinum-DNA GG diadducts, uracil, dihydrouracil and abasic sites. This is the first time that a single DNA repair endonuclease with the ability to recognize such a diverse range of lesions has been described. This study suggests that Uve1p and the alternative excision repair pathway may participate broadly in the repair of DNA damage.
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UVDE from Schizosaccharomyces pombe has broad substrate specificity including both CPDs and 6-4 PPs and initiates the nucleotide incision repair (NIR) pathway.
“However, the UV endonuclease (UVDE) from Schizosaccharomyces pombe has a very broad substrate specificity which includes both CPDs and 6–4 PPs and is known to initiate the nucleotide incision repair (NIR) pathway18,19.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [18]
UVDE initiates repair at both dipyrimidine photoproducts by incision immediately 5′ to the damage, followed by long-patch BER in conjunction with Rad27/Fen1, XRCC1, PARP1, and DNA polymerase.
“UVDE initiates repair at both dipyrimidine photoproducts by incision immediately 5′ to the damage18,28,29, followed by long-patch BER in conjunction with Rad27/Fen1, XRCC1, PARP1, and DNA polymerase30–33.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [18]
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Self-citation
- Authors
- Avery, A. M., Kaur, B., Taylor, J.-S., Mello, J. A., Essigmann, J. M., & Doetsch, P. W.
- Affiliations
- Emory University (US)
- Washington University in St. Louis (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Doetsch, P. W.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-01-01
- Volume
- 27
- Issue
- 11
- Pages
- 2256-2264
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC148789
- OpenAlex
- W2158622957
- Cited by
- 54
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2021: 3 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Emory University
- National Cancer Institute (CA 73041, CA 52127, CA40463, R35CA052127, R01CA073041)
- 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 › DNA and Nucleic Acid Chemistry
- Keywords
- Schizosaccharomyces pombe, substrate specificity, cyclobutane pyrimidine dimers, 6-4 photoproducts, Dewar isomers, DNA repair, abasic sites, uracil, dihydrouracil, DNA distortion
- MeSH terms
- DNA Repair, Endodeoxyribonucleases, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Platinum, Pyrimidine Dimers, Pyrimidines, Recombinant Fusion Proteins, Schizosaccharomyces, Substrate Specificity, Ultraviolet Rays, DNA Adducts, Schizosaccharomyces pombe Proteins
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