ArticleThe Journal of biological chemistry2014
The steric gate of DNA polymerase ι regulates ribonucleotide incorporation and deoxyribonucleotide fidelity.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 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
- The A, B, C, D's of replicative DNA polymerase fidelity: utilizing high-throughput single-molecule sequencing to understand the molecular basis for DNA polymerase accuracy.Nucleic acids research · 2025Article
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
- Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.International journal of molecular sciences · 2023Review
- Mechanism of nucleotide discrimination by the translesion synthesis polymerase Rev1.Nature communications · 2022Article
- DNA Polymerase η Promotes the Transcriptional Bypass ofJournal of the American Chemical Society · 2021Article
- Novel Escherichia coli active site dnaE alleles with altered base and sugar selectivity.Molecular microbiology · 2021Article
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021Review
- One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.International journal of molecular sciences · 2020Review
- Response of Sulfolobus solfataricus Dpo4 polymerase in vitro to a DNA G-quadruplex.Mutagenesis · 2019Article
- Human DNA polymerase η has reverse transcriptase activity in cellular environments.The Journal of biological chemistry · 2019Article
- DNA polymerase ι is acetylated in response to SScientific reports · 2019Article
- Current perspectives on mechanisms of ribonucleotide incorporation and processing in mammalian DNA.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2019Review
- Ribonucleotide discrimination by translesion synthesis DNA polymerases.Critical reviews in biochemistry and molecular biology · 2018Review
- Human DNA polymerase η accommodates RNA for strand extension.The Journal of biological chemistry · 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
- DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes.The Journal of experimental medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Accurate DNA synthesis in vivo depends on the ability of DNA polymerases to select dNTPs from a nucleotide pool dominated by NTPs. High fidelity replicative polymerases have evolved to efficiently exclude NTPs while copying long stretches of undamaged DNA. However, to bypass DNA damage, cells utilize specialized low fidelity polymerases to perform translesion DNA synthesis (TLS). Of interest is human DNA polymerase ι (pol ι), which has been implicated in TLS of oxidative and UV-induced lesions. Here, we evaluate the ability of pol ι to incorporate NTPs during DNA synthesis. pol ι incorporates and extends NTPs opposite damaged and undamaged template bases in a template-specific manner. The Y39A "steric gate" pol ι mutant is considerably more active in the presence of Mn(2+) compared with Mg(2+) and exhibits a marked increase in NTP incorporation and extension, and surprisingly, it also exhibits increased dNTP base selectivity. Our results indicate that a single residue in pol ι is able to discriminate between NTPs and dNTPs during DNA synthesis. Because wild-type pol ι incorporates NTPs in a template-specific manner, certain DNA sequences may be "at risk" for elevated mutagenesis during pol ι-dependent TLS. Molecular modeling indicates that the constricted active site of wild-type pol ι becomes more spacious in the Y39A variant. Therefore, the Y39A substitution not only permits incorporation of ribonucleotides but also causes the enzyme to favor faithful Watson-Crick base pairing over mutagenic configurations.
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