ArticleNucleic acids research2013
Human polymerase kappa uses a template-slippage deletion mechanism, but can realign the slipped strands to favour base substitution mutations over deletions.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Methylglyoxal mutagenizes single-stranded DNA via Rev1-associated slippage and mispairing.Nucleic acids research · 2025Article
- Methylglyoxal mutagenizes single-stranded DNA via Rev1-associated slippage and mispairing.bioRxiv : the preprint server for biology · 2025Article
- Review
- Revisiting mutagenesis at non-B DNA motifs in the human genome.Nature structural & molecular biology · 2023Article
- Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis.PLoS genetics · 2022Article
- Article
- Identification and Characterization of Thermostable Y-Family DNA Polymerases η, ι, κ and Rev1 From a Lower Eukaryote,Frontiers in molecular biosciences · 2021Article
- 5-Formylcytosine mediated DNA-protein cross-links block DNA replication and induce mutations in human cells.Nucleic acids research · 2018Article
- Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ.Chemical research in toxicology · 2017Article
- Hypermutation signature reveals a slippage and realignment model of translesion synthesis by Rev3 polymerase in cisplatin-treated yeast.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Local DNA dynamics shape mutational patterns of mononucleotide repeats in human genomes.Nucleic acids research · 2015Article
- An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Recent insight into the kinetic mechanisms and conformational dynamics of Y-Family DNA polymerases.Biochemistry · 2014Review
- Three residues of the interdomain linker determine the conformation and single-base deletion fidelity of Y-family translesion polymerases.The Journal of biological chemistry · 2014Article
- Role of DNA polymerase κ in the maintenance of genomic stability.Molecular & cellular oncology · 2014Review
- Handling the 3-methylcytosine lesion by six human DNA polymerases members of the B-, X- and Y-families.Nucleic acids research · 2014Article
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3 authors.
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Abstract
Polymerases belonging to the DinB class of the Y-family translesion synthesis DNA polymerases have a preference for accurately and efficiently bypassing damaged guanosines. These DinB polymerases also generate single-base (-1) deletions at high frequencies with most occurring on repetitive 'deletion hotspot' sequences. Human DNA polymerase kappa (hPolκ), the eukaryotic DinB homologue, displays an unusual efficiency for to extend from mispaired primer termini, either by extending directly from the mispair or by primer-template misalignment. This latter property explains how hPolκ creates single-base deletions in non-repetitive sequences, but does not address how deletions occur in repetitive deletion hotspots. Here, we show that hPolκ uses a classical Streisinger template-slippage mechanism to generate -1 deletions in repetitive sequences, as do the bacterial and archaeal homologues. After the first nucleotide is added by template slippage, however, hPolκ can efficiently realign the primer-template duplex before continuing DNA synthesis. Strand realignment results in a base-substitution mutation, minimizing generation of more deleterious frameshift mutations. On non-repetitive sequences, we find that nucleotide misincorporation is slower if the incoming nucleotide can correctly basepair with the nucleotide immediately 5' to the templating base, thereby competing against the mispairing with the templating base.
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