ArticleProceedings of the National Academy of Sciences of the United States of America2007
What a difference a decade makes: insights into translesion DNA synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers.
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Who cites it
228 citing papers in PubMed, 374 citations in OpenAlex.
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- Genome instability is increased during DNA replication in the presence of the CPD UV photoproduct in transcriptionally active genes.iScience · 2026Article
- Conserved Active Site Loop Residues of E. coli DinB and Human DNA Polymerase Kappa Govern Activity.Environmental and molecular mutagenesis · 2026Article
- Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.bioRxiv : the preprint server for biology · 2026Article
- Implications of DNA damage response and immunotherapy in tumor therapy.Cell communication and signaling : CCS · 2025Review
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- Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.Cancer science · 2024Article
- Effects of the Y432S Cancer-Associated Variant on the Reaction Mechanism of Human DNA Polymerase κ.Journal of chemical information and modeling · 2024Article
- Replication Bypass of theBiochemistry · 2024Article
- A Novel Interaction Between RAD23A/B and Y-family DNA Polymerases.Journal of molecular biology · 2023Article
- Biochemical Activity of 17 Cancer-Associated Variants of DNA Polymerase Kappa Predicted by Electrostatic Properties.Chemical research in toxicology · 2023Article
- Incorporation of inosine into DNA by human polymerase eta (Polη): kinetics of nucleotide misincorporation and structural basis for the mutagenicity.The Biochemical journal · 2023Article
- Thumb-domain dynamics modulate the functional repertoire of DNA-Polymerase IV (DinB).Nucleic acids research · 2023Article
- Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.Molecular and cellular biology · 2023Article
- Establishing Linkages Among DNA Damage, Mutagenesis, and Genetic Diseases.Chemical research in toxicology · 2022Review
168 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Living organisms are continually under attack from a vast array of DNA-damaging agents that imperils their genomic integrity. As a consequence, cells possess an army of enzymes to repair their damaged chromosomes. However, DNA lesions often persist and pose a considerable threat to survival, because they can block the cell's replicase and its ability to complete genome duplication. It has been clear for many years that cells must possess a mechanism whereby the DNA lesion could be tolerated and physically bypassed. Yet it was only within the past decade that specialized DNA polymerases for "translesion DNA synthesis" or "TLS" were identified and characterized. Many of the TLS enzymes belong to the recently described "Y-family" of DNA polymerases. By possessing a spacious preformed active site, these enzymes can physically accommodate a variety of DNA lesions and facilitate their bypass. Flexible DNA-binding domains and a variable binding pocket for the replicating base pair further allow these TLS polymerases to select specific lesions to bypass and favor distinct non-Watson-Crick base pairs. Consequently, TLS polymerases tend to exhibit much lower fidelity than the cell's replicase when copying normal DNA, which results in a dramatic increase in mutagenesis. Occasionally this can be beneficial, but it often speeds the onset of cancer in humans. Cells use both transcriptional and posttranslational regulation to keep these low-fidelity polymerases under strict control and limit their access to a replication fork. Our perspective focuses on the mechanistic insights into TLS by the Y-family polymerases, how they are regulated, and their effects on genomic (in)stability that have been described in the past decade.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.