ArticleNucleic acids research2012
The catalytic cycle for ribonucleotide incorporation by human DNA Pol λ.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- A Comparative Study for the Incorporation of 8-oxo-dATP in DNA by Human DNA Polymerases.International journal of molecular sciences · 2026Article
- Aspergillus fumigatus PolX1 is an early ancestor of vertebrate terminal deoxynucleotidyl transferases.Nucleic acids research · 2026Article
- Deciphering the Role of DNA Polymerase Eta on the Incorporation and Bypass of Inosine and Cell Cycle Arrest.International journal of molecular sciences · 2025Article
- DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining.DNA repair · 2024Article
- Substrate Specificity Diversity of Human Terminal Deoxynucleotidyltransferase May Be a Naturally Programmed Feature Facilitating Its Biological Function.International journal of molecular sciences · 2024Article
- A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides.Nucleic acids research · 2023Article
- Polλ promotes microhomology-mediated end-joining.Nature structural & molecular biology · 2023Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
- Mechanism of nucleotide discrimination by the translesion synthesis polymerase Rev1.Nature communications · 2022Article
- Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.Nature communications · 2021Article
- The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides.Scientific reports · 2021Article
- Article
- DNA polymerase mu: An inflexible scaffold for substrate flexibility.DNA repair · 2020Review
- Ribonucleotide incorporation in yeast genomic DNA shows preference for cytosine and guanosine preceded by deoxyadenosine.Nature communications · 2020Article
- A polar filter in DNA polymerases prevents ribonucleotide incorporation.Nucleic acids research · 2019Article
- Human DNA polymerase η has reverse transcriptase activity in cellular environments.The Journal of biological chemistry · 2019Article
- Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining.Science (New York, N.Y.) · 2018Article
- Ribonucleotide discrimination by translesion synthesis DNA polymerases.Critical reviews in biochemistry and molecular biology · 2018Review
- Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although most DNA polymerases discriminate against ribonucleotide triphosphaets (rNTPs) during DNA synthesis, recent studies have shown that large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome. Here, we investigate how a DNA polymerase can stably incorporate an rNTP. The X-ray crystal structure of a variant of human DNA polymerase λ reveals that the rNTP occupies the nucleotide binding pocket without distortion of the active site, despite an unfavorable interaction between the 2'-O and Tyr505 backbone carbonyl. This indicates an energetically unstable binding state for the rNTP, stabilized by additional protein-nucleotide interactions. Supporting this idea is the 200-fold lower catalytic efficiency for rNTP relative to deoxyribonucleotide triphosphate (dNTP) incorporation, reflecting a higher apparent Km value for the rNTP. Furthermore, distortion observed in the structure of the post-catalytic product complex suggests that once the bond between the α- and β-phosphates of the rNTP is broken, the unfavorable binding state of the ribonucleotide cannot be maintained. Finally, structural and biochemical evaluation of dNTP insertion onto an ribonucleotide monophosphate (rNMP)-terminated primer indicates that a primer-terminal rNMP does not impede extension. The results are relevant to how ribonucleotides are incorporated into DNA in vivo, during replication and during repair, perhaps especially in non-proliferating cells when rNTP:dNTP ratios are high.
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Registered trials
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.