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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“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.
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“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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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
The Escherichia coli dnaB replication protein is a DNA helicase.
LeBowitz, J. H., & McMacken, R. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38564-2 · Cited by 504
A phylogenomic study of DNA repair genes, proteins, and processes
Eisen, J. A., & Hanawalt, P. C. (1999) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(99)00050-6 · Cited by 469
Reijns, M. A. M., Rabe, B., Rigby, R. E., Mill, P., Astell, K. R., Lettice, L. A., Boyle, S., Leitch, A., Keighren, M., Kilanowski, F., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.011 · Cited by 466
Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases
McElhinny, S. A. N., Watts, B. E., Kumar, D., Watt, D. L., Lundström, E.-B., Burgers, P., Johansson, E., Chabes, A., & Kunkel, T. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914857107 · Cited by 418
Genome instability due to ribonucleotide incorporation into DNA
McElhinny, S. A. N., Kumar, D., Clark, A. B., Watt, D. L., Watts, B. E., Lundström, E.-B., Johansson, E., Chabes, A., & Kunkel, T. A. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.424 · Cited by 407
Characterization of Nucleotide Pools as a Function of Physiological State in Escherichia coli
Buckstein, M. H., He, J., & Rubin, H. (2008) · Journal of Bacteriology · doi:10.1128/jb.01020-07 · Cited by 370
RNase H2-Initiated Ribonucleotide Excision Repair
Sparks, J. L., Chon, H., Cerritelli, S. M., Kunkel, T. A., Johansson, E., Crouch, R. J., & Burgers, P. M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.035 · Cited by 339
Mutagenic Processing of Ribonucleotides in DNA by Yeast Topoisomerase I
Kim, N., Huang, S.-Y. N., Williams, J. S., Li, Y. C., Clark, A. B., Cho, J.-E., Kunkel, T. A., Pommier, Y., & Jinks-Robertson, S. (2011) · Science · doi:10.1126/science.1205016 · Cited by 291
DNA修復遺伝子,タンパクと過程のphylogenomic(系統発生的ゲノム)調査
Eisen, J. A., & Hanawalt, P. C. (1999) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · Cited by 269
PCNA function in the activation and strand direction of MutLα endonuclease in mismatch repair
Pluciennik, A., Dzantiev, L., Iyer, R. R., Constantin, N., Kadyrov, F. A., & Modrich, P. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010662107 · Cited by 259
Saccharomyces cerevisiae MutLα Is a Mismatch Repair Endonuclease
Kadyrov, F. A., Holmes, S. F., Arana, M. E., Lukianova, O. A., O’Donnell, M. E., Kunkel, T. A., & Modrich, P. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707617200 · Cited by 247
Self-citationChoosing the right sugar: How polymerases select a nucleotide substrate
Joyce, C. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.5.1619 · Cited by 222
Characterization of a Triple DNA Polymerase Replisome
McInerney, P., Johnson, A. M., Katz, F. S., & O’Donnell, M. E. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.019 · Cited by 189
Self-citationPolymerase Mu Is a DNA-Directed DNA/RNA Polymerase
McElhinny, S. A. N., & Ramsden, D. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.7.2309-2315.2003 · Cited by 179
Ohtani, N., Haruki, M., Morikawa, M., Crouch, R. J., Itaya, M., & Kanaya, S. (1998) · Biochemistry · doi:10.1021/bi982207z · Cited by 172
Miyabe, I., Kunkel, T. A., & Carr, A. M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002407 · Cited by 162
Structure of the Endonuclease Domain of MutL: Unlicensed to Cut
Pillon, M. C., Lorenowicz, J. J., Uckelmann, M., Klocko, A. D., Mitchell, R. R., Chung, Y. S., Modrich, P. L., Walker, G. C., Simmons, L. A., Friedhoff, P., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.027 · Cited by 139
Self-citationGINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
Sekedat, M. D., Fenyö, D., Rogers, R. S., Tackett, A. J., Aitchison, J. D., & Chait, B. T. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.8 · Cited by 119
Independence of replisomes in Escherichia coli chromosomal replication
Breier, A. M., Weier, H. G., & Cozzarelli, N. R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500812102 · Cited by 108
Larrea, A. A., Lujan, S. A., & Kunkel, T. A. (2010) · Cell · doi:10.1016/j.cell.2010.05.002 · Cited by 106
Isolation of RNase H Genes That Are Essential for Growth of Bacillus subtilis 168
Itaya, M., Omori, A., Kanaya, S., Crouch, R. J., Tanaka, T., & Kondo, K. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.7.2118-2123.1999 · Cited by 89
Single-molecule studies reveal the function of a third polymerase in the replisome
Georgescu, R. E., Kurth, I., & O’Donnell, M. E. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2179 · Cited by 86
Self-citationDeLucia, A. M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg417 · Cited by 83
The wild‐type Schizosaccharomyces pombe mat1 imprint consists of two ribonucleotides
Vengrova, S., & Dalgaard, J. Z. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400576 · Cited by 71
Lagging Strand Replication Proteins in Genome Stability and DNA Repair
Rossi, M. L., Purohit, V., Brandt, P. D., & Bambara, R. A. (2005) · Chemical Reviews · doi:10.1021/cr040497l · Cited by 65
Zhu, H., & Shuman, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705476200 · Cited by 55
Wang, M., Xia, S., Blaha, G. M., Steitz, T. A., Konigsberg, W. H., & Wang, J. (2010) · Biochemistry · doi:10.1021/bi101192f · Cited by 48
Lenhart, J. S., Sharma, A., Hingorani, M., & Simmons, L. A. (2012) · Molecular Microbiology · doi:10.1111/mmi.12115 · Cited by 40
Self-citationDupes, N. M., Walsh, B. W., Klocko, A. D., Lenhart, J. S., Peterson, H. L., Gessert, D. A., Pavlick, C. E., & Simmons, L. A. (2010) · Journal of Bacteriology · doi:10.1128/jb.01435-09 · Cited by 21
Self-citationResidues in the N-Terminal Domain of MutL Required for Mismatch Repair in Bacillus subtilis
Bolz, N. J., Lenhart, J. S., Weindorf, S. C., & Simmons, L. A. (2012) · Journal of Bacteriology · doi:10.1128/jb.01142-12 · Cited by 20
Self-citationClark, A., & Kunkel, T. A. (2010) · Cell Cycle · doi:10.4161/cc.9.22.14052 · Cited by 7
Research works printed but not linked: 1
- A Kornberg, TA Baker DNA Replication (W. H. Freeman, 2nd Ed, New York, 1992).
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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
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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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