Requirement of Watson-Crick Hydrogen Bonding for DNA Synthesis by Yeast DNA Polymerase η
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Classical high-fidelity DNA polymerases discriminate between the correct and incorrect nucleotides by using geometric constraints imposed by the tight fit of the active site with the incipient base pair. Consequently, Watson-Crick (W-C) hydrogen bonding between the bases is not required for the efficiency and accuracy of DNA synthesis by these polymerases. DNA polymerase eta (Poleta) is a low-fidelity enzyme able to replicate through DNA lesions. Using difluorotoluene, a nonpolar isosteric analog of thymine unable to form W-C hydrogen bonds with adenine, we found that the efficiency and accuracy of nucleotide incorporation by Poleta are severely impaired. From these observations, we suggest that W-C hydrogen bonding is required for DNA synthesis by Poleta; in this regard, Poleta differs strikingly from classical high-fidelity DNA polymerases.
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These ideas are supported by structural information and by a report that the insertion fidelity of yeast Pol η is severely impaired with difluorotoluene, a nonpolar isosteric analog of thymine that is unable to form Watson-Crick hydrogen bonds with adenine.
“These ideas are supported by structural information (20, 21, 26 -28) and by a report (29) that the insertion fidelity of yeast Pol is severely impaired with difluorotoluene, a nonpolar isosteric analog of thymine that is unable to form Watson-Crick hydrogen bonds with adenine.”
From DNA Replication Fidelity (2004) · cites this paper as [29]
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- Authors
- Washington, M. T., Helquist, S. A., Kool, E. T., Prakash, L., & Prakash, S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Stanford University (US)
- Corresponding author
- Prakash, Satya
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-07-01
- Volume
- 23
- Issue
- 14
- Pages
- 5107-5112
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC162216
- OpenAlex
- W2111754594
- Cited by
- 75
- References
- 51
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Update notices
- correction (2003-09-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm019261-30)
- National Institute of General Medical Sciences (GM-19261, GM52956, R01GM052956)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- DNA polymerase eta, Watson-Crick hydrogen bonding, nucleotide incorporation, base pair geometry, yeast
- MeSH terms
- Y-Family DNA Polymerases, DNA, DNA-Directed DNA Polymerase, Fungal Proteins, Hydrogen Bonding, Kinetics, Nucleotides, Toluene, Yeasts
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