The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Cost of rNTP/dNTP pool imbalance at the replication fork
Open accessAbstract
The concentration of ribonucleoside triphosphates (rNTPs) in cells is far greater than the concentration of deoxyribonucleoside triphosphates (dNTPs), and this pool imbalance presents a challenge for DNA polymerases (Pols) to select their proper substrate. This report examines the effect of nucleotide pool imbalance on the rate and fidelity of the Escherichia coli replisome. We find that rNTPs decrease replication fork rate by competing with dNTPs at the active site of the C-family Pol III replicase at a step that does not require correct base-pairing. The effect of rNTPs on Pol rate generalizes to B-family eukaryotic replicases, Pols δ and ε. Imbalance of the dNTP pool also slows the replisome and thus is not specific to rNTPs. We observe a measurable frequency of rNMP incorporation that predicts one rNTP incorporated every 2.3 kb during chromosome replication. Given the frequency of rNMP incorporation, the repair of rNMPs is likely rapid. RNase HII nicks DNA at single rNMP residues to initiate replacement with dNMP. Considering that rNMPs will mark the new strand, RNase HII may direct strand-specificity for mismatch repair (MMR). How the newly synthesized strand is recognized for MMR is uncertain in eukaryotes and most bacteria, which lack a methyl-directed nicking system. Here we demonstrate that Bacillus subtilis incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the RNase HII gene deletion enhances mutagenesis, suggesting a possible role of incorporated rNMPs in MMR.
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both replicative and translesion DNA polymerases make sugar errors”
From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“rNMPs may represent the most common nucleotide requiring removal from genomic DNA in organisms spanning all domains of life”
From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“it has been estimated that E. coli Pol III holoenzyme incorporates up to 2000 rNMPs per one round of chromosomal replication in vitro”
From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013
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Citations
Cites
1 retracted
Polymerase Exchange During Okazaki Fragment Synthesis Observed in Living Cells
Lia, G., Michel, B., & Allemand, J. (2011) · Science · doi:10.1126/science.1210400 · Cited by 56
RetractedFriedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. (2005) · doi:10.1128/9781555816704 · Cited by 5,683
Physiological concentrations of purines and pyrimidines
Traut, T. W. (1994) · Molecular and Cellular Biochemistry · doi:10.1007/bf00928361 · Cited by 1,867
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., & Rabinowitz, J. D. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.186 · Cited by 1,830
DNA Mismatch Repair: Functions and Mechanisms
Iyer, R. R., Pluciennik, A., Burdett, V., & Modrich, P. L. (2005) · Chemical Reviews · doi:10.1021/cr0404794 · Cited by 935
Ribonuclease H: the enzymes in eukaryotes
Cerritelli, S. M., & Crouch, R. J. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06908.x · Cited by 845
Repair and Genetic Consequences of Endogenous DNA Base Damage in Mammalian Cells
Barnes, D. E., & Lindahl, T. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.092448 · Cited by 753
Endonucleolytic Function of MutLα in Human Mismatch Repair
Kadyrov, F. A., Dzantiev, L., Constantin, N., & Modrich, P. L. (2006) · Cell · doi:10.1016/j.cell.2006.05.039 · Cited by 626
Yeast DNA Polymerase ε Participates in Leading-Strand DNA Replication
Pursell, Z. F., Isoz, I., Lundström, E.-B., Johansson, E., & Kunkel, T. A. (2007) · Science · doi:10.1126/science.1144067 · Cited by 565
Division of Labor at the Eukaryotic Replication Fork
McElhinny, S. A. N., Gordenin, D. A., Stith, C. M. W., Burgers, P., & Kunkel, T. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.02.022 · Cited by 528
Research works printed but not linked: 1
- A Kornberg, TA Baker DNA Replication (W. H. Freeman, 2nd Ed, New York, 1992).
Cited by
Sorted by citations
Roles of eukaryotic topoisomerases in transcription, replication and genomic stability
Pommier, Y. G., Sun, Y., Huang, S.-Y. N., & Nitiss, J. L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.111 · Cited by 980
Not breathing is not an option: How to deal with oxidative DNA damage
Markkanen, E. (2017) · DNA repair · doi:10.1016/j.dnarep.2017.09.007 · Cited by 205
Ribonucleotides in DNA: Origins, repair and consequences
Williams, J. S., & Kunkel, T. A. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.03.029 · Cited by 176
A Critical Balance: dNTPs and the Maintenance of Genome Stability
Pai, C., & Kearsey, S. E. (2017) · Genes · doi:10.3390/genes8020057 · Cited by 169
DNA Replication—A Matter of Fidelity
Ganai, R. A., & Johansson, E. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.003 · Cited by 169
Metadata
- Authors
- Yao, N. Y., Schroeder, J. W., Yurieva, O., Simmons, L. A., & O’Donnell, M. E.
- Affiliations
- Rockefeller University (US)
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-07-23
- Volume
- 110
- Issue
- 32
- Pages
- 12942-12947
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3740908
- OpenAlex
- W1967720448
- Cited by
- 114
- References
- 41
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 4 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 8 · 2015: 11 · 2014: 17 · 2013: 1
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of General Medical Sciences (GM38831, T32GM007544, R01GM038839)
- 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
- ribonucleoside triphosphates, DNA replication, DNA polymerase III, RNase HII, DNA mismatch repair, strand specificity, mutagenesis, Escherichia coli, Bacillus subtilis, DNA polymerase delta, DNA polymerase epsilon
- MeSH terms
- Bacillus subtilis, Binding, Competitive, Deoxyribonucleotides, DNA Polymerase III, DNA Repair, DNA Replication, DNA, Bacterial, Electrophoresis, Agar Gel, Escherichia coli, Models, Genetic, Mutation, Protein Binding, Ribonucleotides, Ribonuclease H, Escherichia coli Proteins
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