Error-free replicative bypass of (6–4) photoproducts by DNA polymerase ζ in mouse and human cells
Open accessAbstract
The ultraviolet (UV)-induced (6–4) pyrimidine–pyrimidone photoproduct [(6–4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6–4) TT photoproduct carried on a duplex plasmid where bidirectional replication initiates from an origin of replication. We show that TLS contributes to a large fraction of lesion bypass and that it is mostly error-free. We find that, whereas Pol η and Pol ι provide alternate pathways for mutagenic TLS, surprisingly, Pol ζ functions independently of these Pols and in a predominantly error-free manner. We verify and extend these observations in mouse cells and conclude that, in human cells, TLS during replication can be markedly error-free even opposite a highly distorting DNA lesion.
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Polη may also be involved in bypass of 6-4PPs, as suggested by plasmid assays in yeast and human cells.
“Pol may also be involved in the bypass of 6-4PPs as suggested by plasmids assays performed both in yeast and human cells [26,27].”
From Gap-filling and bypass at the replication fork are both active mechanisms for tolerance of low-dose ultraviolet-induced DNA damage in the human genome (2014) · cites this paper as [26]
Some data suggest Polη can also play a role in bypass of 6-4PPs.
“some data suggest that Pol can also play a role in the bypass of 6-4PPs [26,27]”
From Gap-filling and bypass at the replication fork are both active mechanisms for tolerance of low-dose ultraviolet-induced DNA damage in the human genome (2014) · cites this paper as [26]
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References 22 · Cited by 81
- Authors
- Yoon, J.-H., Prakash, L., & Prakash, S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-01-15
- Volume
- 24
- Issue
- 2
- Pages
- 123-128
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2807347
- OpenAlex
- W2144584734
- Cited by
- 81
- References
- 22
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Beckman Research Institute, City of Hope
- National Cancer Institute (T32CA117834)
- National Institute of Environmental Health Sciences (R01ES012411, P30ES006676, ES-06676, ES 012411)
- 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
- translesion synthesis, DNA polymerase zeta, DNA polymerase eta, DNA polymerase iota, error-free bypass, UV-induced DNA damage, bidirectional replication, mutagenesis
- MeSH terms
- Animals, Cell Line, Cells, Cultured, DNA Damage, DNA-Directed DNA Polymerase, DNA Repair, DNA Replication, Humans, Pyrimidine Dimers, Ultraviolet Rays, Mice
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