ArticleDNA repair2015
Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae.
Article in DNA repair, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Deciphering the Role of DNA Polymerase Eta on the Incorporation and Bypass of Inosine and Cell Cycle Arrest.International journal of molecular sciences · 2025Article
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
- Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021Review
- Selective Metal Ion Utilization Contributes to the Transformation of the Activity of Yeast Polymerase η from DNA Polymerization toward RNA Polymerization.International journal of molecular sciences · 2020Article
- One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.International journal of molecular sciences · 2020Review
- RNase H2-RED carpets the path to eukaryotic RNase H2 functions.DNA repair · 2019Review
- Response of Sulfolobus solfataricus Dpo4 polymerase in vitro to a DNA G-quadruplex.Mutagenesis · 2019Article
- RNase H activities counteract a toxic effect of Polymerase η in cells replicating with depleted dNTP pools.Nucleic acids research · 2019Article
- DNA polymerase η contributes to genome-wide lagging strand synthesis.Nucleic acids research · 2019Article
- Lsm12 Mediates Deubiquitination of DNA Polymerase η To HelpApplied and environmental microbiology · 2019Article
- Ribonucleotide discrimination by translesion synthesis DNA polymerases.Critical reviews in biochemistry and molecular biology · 2018Review
- Rad5 coordinates translesion DNA synthesis pathway by recognizing specific DNA structures in saccharomyces cerevisiae.Current genetics · 2018Article
- Translesion synthesis DNA polymerase η exhibits a specific RNA extension activity and a transcription-associated function.Scientific reports · 2017Article
- Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.Nucleic acids research · 2017Article
- Translesion DNA polymerases in eukaryotes: what makes them tick?Critical reviews in biochemistry and molecular biology · 2017Review
- Ribonucleotide incorporation by human DNA polymerase η impacts translesion synthesis and RNase H2 activity.Nucleic acids research · 2017Article
- Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans.Scientific reports · 2017Article
- Processing ribonucleotides incorporated during eukaryotic DNA replication.Nature reviews. Molecular cell biology · 2016Review
- The Balancing Act of Ribonucleotides in DNA.Trends in biochemical sciences · 2016Review
- Mechanism of Ribonucleotide Incorporation by Human DNA Polymerase η.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA polymerase η (pol η) is best characterized for its ability to perform accurate and efficient translesion DNA synthesis (TLS) through cyclobutane pyrimidine dimers (CPDs). To ensure accurate bypass the polymerase is not only required to select the correct base, but also discriminate between NTPs and dNTPs. Most DNA polymerases have a conserved "steric gate" residue which functions to prevent incorporation of NMPs during DNA synthesis. Here, we demonstrate that the Phe35 residue of Saccharomyces cerevisiae pol η functions as a steric gate to limit the use of ribonucleotides during polymerization both in vitro and in vivo. Unlike the related pol ι enzyme, wild-type pol η does not readily incorporate NMPs in vitro. In contrast, a pol η F35A mutant incorporates NMPs on both damaged and undamaged DNA in vitro with a high degree of base selectivity. An S.cerevisiae strain expressing pol η F35A (rad30-F35A) that is also deficient for nucleotide excision repair (rad1Δ) and the TLS polymerase, pol ζ (rev3Δ), is extremely sensitive to UV-light. The sensitivity is due, in part, to RNase H2 activity, as an isogenic rnh201Δ strain is roughly 50-fold more UV-resistant than its RNH201(+) counterpart. Interestingly the rad1Δ rev3Δ rad30-F35A rnh201Δ strain exhibits a significant increase in the extent of spontaneous mutagenesis with a spectrum dominated by 1bp deletions at runs of template Ts. We hypothesize that the increased mutagenesis is due to rA incorporation at these sites and that the short poly rA tract is subsequently repaired in an error-prone manner by a novel repair pathway that is specifically targeted to polyribonucleotide tracks. These data indicate that under certain conditions, pol η can compete with the cell's replicases and gain access to undamaged genomic DNA. Such observations are consistent with a role for pol η in replicating common fragile sites (CFS) in human cells.
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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.