DNA polymerase β-dependent long patch base excision repair in living cells
Open accessAbstract
We examined a role for DNA polymerase beta (Pol beta) in mammalian long patch base excision repair (LP BER). Although a role for Pol beta is well known in single-nucleotide BER, information on this enzyme in the context of LP BER has been limited. To examine the question of Pol beta involvement in LP BER, we made use of nucleotide excision repair-deficient human XPA cells expressing UVDE (XPA-UVDE), which introduces a nick directly 5' to the cyclobutane pyrimidine dimer or 6-4 photoproduct, leaving ends with 3'-OH and 5'-phosphorylated UV lesion. We observed recruitment of GFP-fused Pol beta to focal sites of nuclear UV irradiation, consistent with a role of Pol beta in repair of UV-induced photoproducts adjacent to a strand break. This was the first evidence of Pol beta recruitment in LP BER in vivo. In cell extract, a 5'-blocked oligodeoxynucleotide substrate containing a nicked 5'-cyclobutane pyrimidine dimer was repaired by Pol beta-dependent LP BER. We also demonstrated Pol beta involvement in LP BER by making use of mouse cells that are double null for XPA and Pol beta. These results were extended by experiments with oligodeoxynucleotide substrates and purified human Pol beta.
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The reaction is carried out by UV damage endonuclease (UVDE).
“The reaction is carried out by an enzyme called UV damage endonuclease (UVDE).”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
The rad2 gene encodes a structure-specific flap endonuclease involved in processing UV damage into single-strand breaks (SSBs).
“The gene encodes a structure-specific flap endonuclease that is involved in processing of UV damage into single-strand breaks (SSBs).”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
In some organisms such as bacteria and yeast, additional excision repair besides BER and NER exists.
“In some organisms such as bacteria and yeast additional excision repair (besides base excision repair (BER) and NER) exist.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
Studies in S. pombe revealed the rad2 gene as an important factor for UVDE-mediated repair.
“Studies in S. pombe revealed the rad2 gene as an important factor for UVDE-mediated repair.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
UVER may play a crucial role in repair of photoproducts as it removes CPDs more rapidly than NER, especially on the transcribed strand.
“UVER may play a crucial role in repair of photoproducts as it removes CPDs more rapidly than NER, especially on the transcribed strand.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
UVDE introduces a nick on the 5′ end of photoproducts, leaving a 5′-P-UV lesion and a 3′-OH end.
“UVDE introduces a nick on the 5′ end of the photoproducts, leaving a 5′-P-UV lesion and a 3′-OH end.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
UVDE introduces nicks immediately 5′ to specific types of lesions (CPDs, 6′-4′PP, base damage, and others) and initiates UVDE-mediated excision repair (UVER or UVDR).
“UVDE introduces nicks immediately 5′ to specific type of lesions (CPDs, 6′-4′PP, base damage, and others) and initiates UVDE-mediated excision repair (UVER or UVDR).”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
The free 3′-hydroxyl group is a substrate for excision repair strand displacement DNA synthesis.
“The free 3′-hydroxyl group is a substrate for excision repair strand displacement DNA synthesis.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
UVER is rapid and functions properly even in the absence of NER.
“The repair is rapid and functions properly even in the absence of NER.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
The major disadvantage of UVER is the great number of nicks introduced in the DNA strand that may comprise an obstacle for replication.
“The major disadvantage of UVER is certainly the great number of nicks introduced in the DNA strand that may comprise an obstacle for replication process [85,86,87].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
6′-4′PP are removed more efficiently than CPDs, suggesting an important role of UVER in damage removal.
“Moreover, 6′-4′PP are removed more efficiently than CPDs suggesting important role of UVER in the damage removal.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [85]
In UV-irradiated XPA cells expressing Neurospora crassa UVDE, single-strand breaks were introduced immediately following irradiation and were efficiently repaired, resulting in enhanced survival approaching that of wild-type cells.
“Further, in UV-irradiated XPA cells expressing the Neurospora crassa UVDE, single-strand breaks were introduced immediately following irradiation and were efficiently repaired, resulting in enhanced survival approaching that of wild-type cells31,32.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [31]
Following UVB irradiation, UVDE-initiated repair results in rapid, long-patch processes, improving survival in DNA repair-deficient cells.
“Collectively, these data present consistent evidence that following UVB irradiation, UVDE-initiated repair results in rapid, long-patch processes, improving survival in DNA repair-deficient cells.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [31]
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Excision repair deficiencies in man and mice; lessons from CSA and Fen1 mutants
Kleppa, L. (2011) · NORA - Norwegian Open Research Archives
Shahi, A., Zhao, S., & Kidane, D. (2026) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2025.15360
Jacobs, B., Ivanov, D., Barraza, I., Faulk, C. D., Booth, C. J., Mattos-Canedo, R., Tian, L., DePietro, K., Uzun, A., Roos, W. P., et al. (2026) · Biomolecules · doi:10.3390/biom16030412
Self-citationInterplay Between Base Editing and DNA repair: From Molecular Mechanisms to Clinical Translation
Tao, R., Li, M., Luo, T., & Yao, S. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.109018
- Authors
- Asagoshi, K., Liu, Y., Masaoka, A., Lan, L., Prasad, R., Horton, J. K., Brown, A. R., Wang, X.-H., Bdour, H. M., Sobol, R. W., Taylor, J.-S., Yasui, A., & Wilson, S. H.
- Affiliations
- National Institutes of Health (US)
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- Tohoku University (JP)
- Corresponding author
- Wilson, Samuel H.
- ORCID
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 9
- Issue
- 2
- Pages
- 109-119
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- PMC
- PMC2819632
- OpenAlex
- W1967658193
- Cited by
- 51
- References
- 35
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 6
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- American Cancer Society (1 P20 CA132385-01, 1 R01 AG24364-01, CA40463)
- National Institute of Environmental Health Sciences (RSG-05-246-01-GMC, Z01-ES050158, Z01-ES050159)
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA polymerase beta, long-patch base excision repair, nucleotide excision repair, XPA, cyclobutane pyrimidine dimers, 6-4 photoproducts, UV-induced DNA damage, strand breaks
- MeSH terms
- Animals, Base Sequence, Cell Extracts, Cell Line, Cell Survival, DNA Repair, Endonucleases, Humans, Molecular Sequence Data, Oligonucleotides, Protein Binding, Pyrimidine Dimers, Ultraviolet Rays, Immunoblotting, Polymerase Chain Reaction, DNA Polymerase beta, Flap Endonucleases, Mice, Xeroderma Pigmentosum Group A Protein
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