Y-family DNA polymerases and their role in tolerance of cellular DNA damage
Open accessAbstract
The past 15 years have seen an explosion in our understanding of how cells replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis. This family of polymerases has unique features that enable them to synthesize DNA past damaged bases. However, as they exhibit low fidelity when copying undamaged DNA, it is essential that they are only called into play when they are absolutely required. Several layers of regulation ensure that this is achieved.
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POLH encodes pol eta, which mediates replicative bypass of UV-induced CPD.
“POLH, encoding pol eta which is known to mediate replicative bypass of UV-induced CPD (38)”
From A genome-wide screen reveals that Dyrk1A kinase promotes nucleotide excision repair by preventing aberrant overexpression of cyclin D1 and p21 (2023) · cites this paper as [38]
TLS is the most studied tolerance pathway in human cells and involves specialized translesion polymerases that can use damaged DNA as templates.
“The most studied tolerance pathway in human cells is translesion DNA synthesis (TLS), a process involving specialized translesion polymerases capable of using damaged DNA as replicative templates [7].”
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 [7]
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- [107]Terai K Abbas T Jazaeri AA Dutta A CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis Mol. Cell 2010 37 143 149 20129063 PMC2818832
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- Authors
- Sale, J. E., Lehmann, A. R., & Woodgate, R.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Sussex (GB)
- National Institutes of Health (US)
- Corresponding author
- Sale, Julian E.
- Lehmann, Alan R.
- Woodgate, Roger
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2012-02-23
- Volume
- 13
- Issue
- 3
- Pages
- 141-152
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC3630503
- OpenAlex
- W1980745500
- Cited by
- 665
- References
- 135
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 38 · 2023: 30 · 2022: 35 · 2021: 41 · 2020: 55 · 2019: 36 · 2018: 37 · 2017: 62 · 2016: 59 · 2015: 59 · 2014: 75 · 2013: 48 · 2012: 35
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD001500)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- Y-family DNA polymerases, translesion synthesis, DNA damage tolerance, DNA replication, mutagenesis, polymerase fidelity
- MeSH terms
- Animals, Bacterial Proteins, DNA Damage, DNA Repair, DNA Replication, Humans, Nucleotidyltransferases, Protein Binding, Mutagenesis, Protein Structure, Tertiary, Catalytic Domain
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