ArticleNucleic acids research2014
Handling the 3-methylcytosine lesion by six human DNA polymerases members of the B-, X- and Y-families.
Article in Nucleic acids research, 2014. 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, 49 citations in OpenAlex.
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.Nucleic acids research · 2025Article
- Effect of methyl DNA adducts on 3'-5' exonuclease activity of human TREX1.The Biochemical journal · 2025Article
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.bioRxiv : the preprint server for biology · 2024Article
- Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family.Current issues in molecular biology · 2024Review
- Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-MChemical research in toxicology · 2021Article
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- DNA direct reversal repair and alkylating agent drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Time for remodeling: SNF2-family DNA translocases in replication fork metabolism and human disease.DNA repair · 2020Review
- The Human RAD5 Homologs, HLTF and SHPRH, Have Separate Functions in DNA Damage Tolerance Dependent on The DNA Lesion Type.Biomolecules · 2020Article
- DNA polymerase ι is acetylated in response to SScientific reports · 2019Article
- Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity.Nature genetics · 2018Article
- Ribonucleotide incorporation by human DNA polymerase η impacts translesion synthesis and RNase H2 activity.Nucleic acids research · 2017Article
- OChemical research in toxicology · 2016Article
- Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair.Nature communications · 2016Article
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Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkylating agents often generate 3-methylcytosine (3meC) lesions that are efficiently repaired by AlkB homologues. If AlkB homologue proteins are not functional, or the number of 3meC lesions exceeds the cellular repair capacity, the damage will persist in the genome and become substrate of DNA polymerases (Pols). Though alkylating agents are present in our environment and used in the clinics, currently nothing is known about the impact of 3meC on the accuracy and efficiency of human Pols. Here we compared the 3meC bypass properties of six human Pols belonging to the three families: B (Pol δ), X (Pols β and λ) and Y (Pols κ, ι and η). We show that under replicative conditions 3meC impairs B-family, blocks X-family, but not Y-family Pols, in particular Pols η and ι. These Pols successfully synthesize opposite 3meC; Pol ι preferentially misincorporates dTTP and Pol η dATP. The most efficient extenders from 3meC base-paired primers are Pols κ and η. Finally, using xeroderma pigmentosum variant patient cell extracts, we provide evidence that the presence of functional Pol η is mandatory to efficiently overcome 3meC by mediating complete bypass or extension. Our data suggest that Pol η is crucial for efficient 3meC bypass.
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