Polymerases in nonhomologous end joining: Building a bridge over broken chromosomes
Open accessAbstract
Repair of double-strand breaks in chromosomal DNA is essential. Unfortunately, a paradigm central to most DNA repair pathways--damaged DNA is replaced by polymerases, by using an intact, undamaged complementary strand as a template--no longer works. The nonhomologous end joining (NHEJ) pathway nevertheless still uses DNA polymerases to help repair double-strand breaks. Bacteria use a member of the archaeo-eukaryal primase superfamily, whereas eukaryotes use multiple members of the polymerase X family. These polymerases can, depending on the biologic context, accurately replace break-associated damage, mitigate loss of flanking DNA, or diversify products of repair. Polymerases specifically implicated in NHEJ are uniquely effective in these roles: relative to canonic polymerases, NHEJ polymerases have been engineered to do more with less.
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Nucleotide addition at DNA termini is facilitated by polymerases β, μ, λ.
“Nucleotide addition is facilitated at these termini by multiple polymerases: β, μ, λ [64].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [64]
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Crespan, E., Hübscher, U., & Maga, G. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm568 · Cited by 30 · see citing works
Covo, S., de Villartay, J., Jeggo, P. A., & Livneh, Z. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp703 · Cited by 29 · see citing works
Daley, J. M., & Wilson, T. E. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.07.018 · Cited by 26 · see citing works
Heidenreich, E., & Eisler, H. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.006 · Cited by 25 · see citing works
Human DNA polymerase mu (Pol micro) exhibits an unusual replication slippage ability at AAF lesion
Duvauchelle, J.-B. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.9.2061 · Cited by 23 · see citing works
Kedzierska, K., Thomas, P. G., Venturi, V., Davenport, M. P., Doherty, P. C., Turner, S. J., & Gruta, N. L. L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.4.2556 · Cited by 22 · see citing works
Pol3 is involved in nonhomologous end-joining in Saccharomyces cerevisiae
Chan, C. Y., Galli, A., & Schiestl, R. H. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.05.008 · Cited by 21 · see citing works
Zhou, R., Blanco, L., García–Díaz, M., Bębenek, K., Kunkel, T. A., & Povirk, L. F. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn126 · Cited by 19 · see citing works
Terrados, G., Capp, J., Canitrot, Y., García–Díaz, M., Bębenek, K., Kirchhoff, T., Villanueva, A., Boudsocq, F., Bergoglio, V., Cazaux, C., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007290 · Cited by 19 · see citing works
Sterling, C. H., & Sweasy, J. B. (2005) · Genetics · doi:10.1534/genetics.105.049254 · Cited by 10 · see citing works
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Modernizing the Nonhomologous End-Joining Repertoire: Alternative and Classical NHEJ Share the Stage
Deriano, L., & Roth, D. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155540 · Cited by 448 · see citing works
Darmon, E., & Leach, D. R. F. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00035-13 · Cited by 409 · see citing works
Thompson, L. H. (2012) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2012.06.002 · Cited by 357 · see citing works
Choosing the right path: Does DNA-PK help make the decision?
Neal, J. A., & Meek, K. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.02.010 · Cited by 143 · see citing works
DNA ligase IV syndrome; a review
Altmann, T., & Gennery, A. R. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0520-1 · Cited by 135 · see citing works
Role of non-homologous end joining in V(D)J recombination
Malu, S., Malshetty, V. S., Francis, D. B., & Cortés, P. (2012) · Immunologic Research · doi:10.1007/s12026-012-8329-z · Cited by 92 · see citing works
Plugged into the Ku-DNA hub: The NHEJ network
Frit, P., Ropars, V., Modesti, M., Charbonnier, J., & Calsou, P. (2019) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2019.03.001 · Cited by 81 · see citing works
Promiscuous DNA synthesis by human DNA polymerase θ
Hogg, M., Sauer-Eriksson, A. E., & Johansson, E. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1102 · Cited by 71 · see citing works
The role of DNA damage and repair in liver cancer
Gillman, R., Floro, K. L., Wankell, M., & Hebbard, L. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188493 · Cited by 59 · see citing works
Loc'h, J., & Delarue, M. H. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.03.019 · Cited by 57 · see citing works
Ribonucleotides and manganese ions improve non-homologous end joining by human Polµ
Martín, M. J., García‐Ortiz, M. V., Esteban, V., & Blanco, L. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1444 · Cited by 52 · see citing works
A quantitative model of the major pathways for radiation-induced DNA double-strand break repair
Belov, O., Krasavin, E. A., Lyashko, M. S., Batmunkh, M., & Sweilam, N. H. (2014) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2014.09.024 · Cited by 45 · see citing works
Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu
Moon, A. F., Pryor, J. M., Ramsden, D. A., Kunkel, T. A., Bębenek, K., & Pedersen, L. C. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx527 · Cited by 40 · see citing works
Self-citationCoordination of DNA-PK activation and nuclease processing of DNA termini in NHEJ
Pawelczak, K. S., Bennett, S. M., & Turchi, J. J. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3368 · Cited by 33 · see citing works
Insights into Eukaryotic Primer Synthesis from Structures of the p48 Subunit of Human DNA Primase
Vaithiyalingam, S., Arnett, D. R., Aggarwal, A. K., Eichman, B. F., Fanning, E., & Chazin, W. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.11.007 · Cited by 32 · see citing works
20 years of DNA Polymerase μ, the polymerase that still surprises
Ghosh, D., & Raghavan, S. C. (2021) · FEBS Journal · doi:10.1111/febs.15852 · Cited by 31 · see citing works
The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination
Libri, A., Marton, T., & Deriano, L. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2021.823943 · Cited by 25 · see citing works
DNA-binding determinants promoting NHEJ by human Polµ
Martín, M. J., Juárez, R., & Blanco, L. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks896 · Cited by 26 · see citing works
de Ory, A., Nagler, K., Carrasco, B., Raguse, M., Zafra, O., Moeller, R., & de Vega, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw054 · Cited by 23 · see citing works
DNA Polymerase λ Inactivation by Oxidized Abasic Sites
Stevens, A. J., Guan, L., Bębenek, K., Kunkel, T. A., & Greenberg, M. M. (2013) · Biochemistry · doi:10.1021/bi301592x · Cited by 20 · see citing works
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SAMHD1 restrains aberrant nucleotide insertions at repair junctions generated by DNA end joining
Akimova, E., Gassner, F. J., Schubert, M., Rebhandl, S., Arzt, C., Rauscher, S., Tober, V., Zaborsky, N., Greil, R., & Geisberger, R. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab051 · Cited by 19 · see citing works
Martín, M. J., & Blanco, L. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku475 · Cited by 16 · see citing works
Kumari, N., Antil, H., Kumari, S., & Raghavan, S. C. (2023) · Genomics · doi:10.1016/j.ygeno.2023.110731 · Cited by 15 · see citing works
Suzuki, T., Grúz, P., Honma, M., Adachi, N., & Nohmi, T. (2016) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2016.08.004 · Cited by 13 · see citing works
Resolution of complex ends by Nonhomologous end joining - better to be lucky than good?
Strande, N. T., Waters, C. A., & Ramsden, D. A. (2012) · Genome Integrity · doi:10.1186/2041-9414-3-10 · Cited by 13 · see citing works
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Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis
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The BRCT domain and the specific loop 1 of human Polμ are targets of Cdk2/cyclin A phosphorylation
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REV7: a small but mighty regulator of genome maintenance and cancer development
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DNA Double-Strand Break Repair by Non-homologous End Joining and Its Clinical Relevance
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DNA double-strand break response at a glance
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- Authors
- Ramsden, D. A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Ramsden, Dale A.
- ORCID
- Ramsden, Dale A.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2011-06
- Volume
- 14
- Issue
- 12
- Pages
- 2509-2519
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC3113452
- OpenAlex
- W2024164424
- Cited by
- 51
- References
- 110
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Leukemia and Lymphoma Society
- National Cancer Institute (U01CA097096, CA-97096, R01CA097096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- non-homologous end joining, DNA polymerase, DNA double-strand break repair, DNA end joining, bacterial DNA repair, eukaryotic DNA repair
- MeSH terms
- Animals, DNA, DNA-Directed DNA Polymerase, DNA Repair, Recombination, Genetic, DNA Breaks, Double-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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