Mutagenic cost of ribonucleotides in bacterial DNA
Open accessAbstract
Significance: DNA polymerases frequently incorporate ribonucleotides in place of deoxyribonucleotides during genome replication. RNase HII is responsible for initiating the removal of ribonucleotide errors across all three domains of life. Ribonucleotides that persist in genomic DNA due to defects in RNase HII result in strand breaks, mutagenesis, and neurodevelopmental disease in humans. Here, we define the proteins important for ribonucleotide excision repair in Bacillus subtilis and use genome-wide mutational profiling to determine the mutagenic cost of ribonucleotides in RNase HII-deficient cells. We show that the absence of RNase HII yields error-prone ribonucleotide correction via a pathway that relies on an essential DNA polymerase. We further demonstrate that error-prone ribonucleotide removal causes sequence context-dependent GC → AT transitions on the lagging strand.
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Deletion of RNase HII in B. subtilis results in a 2-fold increase in GC-to-AT transitions.
“Deletion of Ribonuclease HII (RNase HII) (see below) in B. subtilis results in a 2-fold increase in GC-to-AT transitions”
From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Schroeder et al. 2017
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- Authors
- Schroeder, J. W., Randall, J. R., Hirst, W. G., O’Donnell, M. E., & Simmons, L. A.
- Affiliations
- University of Michigan (US)
- Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065
- Corresponding author
- Simmons, Lyle A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-10-16
- Volume
- 114
- Issue
- 44
- Pages
- 11733-11738
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5676920
- OpenAlex
- W2766714943
- Cited by
- 37
- References
- 38
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 1
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-11-27)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Office of Extramural Research, National Institutes of Health (GM107312, T32 GM007544, T32 GM008353)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- RNase HII, ribonucleotide excision repair, mutagenesis, Bacillus subtilis, DNA polymerase, G:C to A:T transitions, lagging strand, neurodevelopmental disorders
- MeSH terms
- Bacillus subtilis, Bacterial Proteins, Base Sequence, DNA Polymerase I, DNA, Bacterial, Models, Biological, Mutation, Ribonucleotides, Gene Expression Regulation, Bacterial, Gene Expression Regulation, Enzymologic, Mutagenesis, Ribonuclease H
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