The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
A role for DNA polymerase θ in the timing of DNA replication
Open accessAbstract
Although DNA polymerase θ (Pol θ) is known to carry out translesion synthesis and has been implicated in DNA repair, its physiological function under normal growth conditions remains unclear. Here we present evidence that Pol θ plays a role in determining the timing of replication in human cells. We find that Pol θ binds to chromatin during early G1, interacts with the Orc2 and Orc4 components of the Origin recognition complex and that the association of Mcm proteins with chromatin is enhanced in G1 when Pol θ is downregulated. Pol θ-depleted cells exhibit a normal density of activated origins in S phase, but early-to-late and late-to-early shifts are observed at a number of replication domains. Pol θ overexpression, on the other hand, causes delayed replication. Our results therefore suggest that Pol θ functions during the earliest steps of DNA replication and influences the timing of replication initiation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
POLQ mRNA is not significantly induced by UVC irradiation, although its expression decreases sharply in UV-irradiated p53-silenced XP-C cells.
“In contrast, the mRNA expression of pol theta (POLQ), a polymerase that is important for the firing of new replication origins ( 32 ), is not significantly induced by UVC irradiation, although its expression decreases sharply in UV-irradiated p53-silenced XP-C cells ( Supplementary Figure S4 ).”
From Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells (2017) · cites this paper as [32]
The citation is attached to the description of POLQ’s role in replication, not to the UVC-expression results, which the citing sentence attributes to its own Supplementary Figure S4. The source’s Results and Discussion support a role for POLQ in the timing of origin activation, but the Results report unchanged active-origin density after POLQ depletion and conclude that depletion did not increase origin firing. They do not establish that POLQ is important for firing new origins. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Galaxy: a platform for interactive large-scale genome analysis.Preprint
Giardine, B., Riemer, C., Hardison, R., Burhans, R. C., Elnitski, L., Shah, P., Zhang, Y., Blankenberg, D., Albert, I., Taylor, J., et al. (2005) · Genome Research · doi:10.1101/gr.4086505 · Cited by 2,217
DNA Replication in Eukaryotic Cells
Bell, S. P., & Dutta, A. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135425 · Cited by 2,065
Méndez, J., & Stillman, B. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8602-8612.2000 · Cited by 923
Durkin, S. G., & Glover, T. W. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.042007.165900 · Cited by 734
Signatures of mutation and selection in the cancer genome
Bignell, G. R., Greenman, C. D., Davies, H., Butler, A. P., Edkins, S., Andrews, J. M., Buck, G., Chen, L., Beare, D., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08768 · Cited by 707
Dynamic Molecular Combing: Stretching the Whole Human Genome for High-Resolution Studies
Michalet, X., Ekong, R., Fougerousse, F., Rousseaux, S., Schurra, C., Hornigold, N., van Slegtenhorst, M., Wolfe, J., Povey, S., Beckmann, J. S., et al. (1997) · Science · doi:10.1126/science.277.5331.1518 · Cited by 611
Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation
Hiratani, I., Ryba, T., Itoh, M., Yokochi, T., Schwaiger, M., Chang, C., Lyou, Y., Townes, T. M., Schübeler, D., & Gilbert, D. M. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060245 · Cited by 576
Isochores and the evolutionary genomics of vertebrates
Bernardi, G. (2000) · Gene · doi:10.1016/s0378-1119(99)00485-0 · Cited by 575
A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation.Preprint
Hardy, C. F., Sussel, L., & Shore, D. (1992) · Genes & Development · doi:10.1101/gad.6.5.801 · Cited by 470
Besnard, E., Babled, A., Lapasset, L., Milhavet, O., Parrinello, H., Dantec, C., Marin, J., & Lemaı̂tre, J.-M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2339 · Cited by 468
Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site
Letessier, A., Millot, G. A., Koundrioukoff, S., Lachagès, A.-M., Vogt, N., Hansen, R. S., Malfoy, B., Brison, O., & Debatisse, M. (2011) · Nature · doi:10.1038/nature09745 · Cited by 414
A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice
Shima, N., Alcaraz, A., Liachko, I., Buske, T. R., Andrews, C. A., Munroe, R. J., Hartford, S. A., Tye, B., & Schimenti, J. C. (2006) · Nature Genetics · doi:10.1038/ng1936 · Cited by 328
Rif1 regulates the replication timing domains on the human genome
Yamazaki, S., Ishii, A., Kanoh, Y., Oda, M., Nishito, Y., & Masai, H. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.180 · Cited by 264
Mouse Rif1 is a key regulator of the replication‐timing programme in mammalian cells
Cornacchia, D., Dileep, V., Quivy, J., Foti, R., Tili, F., Santarella‐Mellwig, R., Antony, C., Almouzni, G., Gilbert, D. M., & Buonomo, S. B. C. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.214 · Cited by 263
Chan, S. H., Yu, A. M., & McVey, M. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001005 · Cited by 253
Rif1 is a global regulator of timing of replication origin firing in fission yeastPreprint
Hayano, M., Kanoh, Y., Matsumoto, S., et al. (2012) · Genes & Development · doi:10.1101/gad.178491.111 · Cited by 252
Cohesin organizes chromatin loops at DNA replication factoriesPreprint
Guillou, E., Ibarra, A., Coulon, V., Casado‐Vela, J., Rico, D., Casal, J. I., Schwob, É., Losada, A., & Méndez, J. (2010) · Genes & Development · doi:10.1101/gad.608210 · Cited by 249
Lemée, F., Bergoglio, V., Fernandez-Vidal, A., Machado-Silva, A., Pillaire, M., Bieth, A., Gentil, C., Baker, L., Martin, A., Leduc, C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910759107 · Cited by 229
Self-citationSilverman, J. S., Takai, H., Buonomo, S. B. C., Eisenhaber, F., & de Lange, T. (2004) · Genes & Development · doi:10.1101/gad.1216004 · Cited by 220
High‐efficiency bypass of DNA damage by human DNA polymerase Q
Seki, M., Masutani, C., Yang, L. W., Schuffert, A., Iwai, S., Bahar, İ., & Wood, R. D. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600424 · Cited by 218
POLQ (Pol ), a DNA polymerase and DNA-dependent ATPase in human cells
Seki, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg814 · Cited by 213
Yu, A., & McVey, M. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq379 · Cited by 198
DNA synthesis by Pol η promotes fragile site stability by preventing under-replicated DNA in mitosis
Bergoglio, V., Boyer, A.-S., Walsh, E. M., Naim, V., Legube, G., Lee, M., Rey, L., Rosselli, F., Cazaux, C., Eckert, K. A., et al. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201207066 · Cited by 197
Self-citationNew insights into replication origin characteristics in metazoans
Cayrou, C., Coulombe, P., Puy, A., Rialle, S., Kaplan, N., Segal, E., & Méchali, M. (2012) · Cell Cycle · doi:10.4161/cc.11.4.19097 · Cited by 185
Low-fidelity DNA synthesis by human DNA polymerase theta
Arana, M. E., Seki, M., Wood, R. D., Rogozin, I. B., & Kunkel, T. A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn310 · Cited by 160
Guilbaud, G., Rappailles, A., Baker, A., Chen, C.-L., Arnéodo, A., Goldar, A., d’Aubenton-Carafa, Y., Thermes, C., Audit, B., & Hyrien, O. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002322 · Cited by 148
Higgins, G. S., Prevo, R., Lee, Y.-F., Helleday, T., Muschel, R. J., Taylor, S., Yoshimura, M., Hickson, I. D., Bernhard, E. J., & McKenna, W. G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4040 · Cited by 148
Establishing the Program of Origin Firing during S Phase in Fission Yeast
Wu, P.-Y. J., & Nurse, P. (2009) · Cell · doi:10.1016/j.cell.2009.01.017 · Cited by 144
Shima, N., Munroe, R. J., & Schimenti, J. C. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.23.10381-10389.2004 · Cited by 144
DNA polymerase θ is preferentially expressed in lymphoid tissues and upregulated in human cancers
Kawamura, K., Bahar, R., Seimiya, M., Chiyo, M., Wada, A., Okada, S., Hatano, M., Tokuhisa, T., Kimura, H., Watanabe, S., et al. (2003) · International Journal of Cancer · doi:10.1002/ijc.11666 · Cited by 140
Modeling genome‐wide replication kinetics reveals a mechanism for regulation of replication timing
Yang, S. C., Rhind, N., & Bechhoefer, J. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.61 · Cited by 135
Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA Damage
Yoshimura, M., Kohzaki, M., Nakamura, J., Asagoshi, K., Sonoda, E., Hou, E. W., Prasad, R., Wilson, S. H., Tano, K., Yasui, A., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.032 · Cited by 132
A ‘DNA replication’ signature of progression and negative outcome in colorectal cancer
Pillaire, M., Sèlves, J., Gordien, K., Gourraud, P., Gentil, C., Danjoux, M., Do, C., Negre, V., Bieth, A., Guimbaud, R., et al. (2009) · Oncogene · doi:10.1038/onc.2009.378 · Cited by 130
Self-citationAllera-Moreau, C., Rouquette, I., Lepage, B., Oumouhou, N., Walschaerts, M., Leconte, E., Schilling, V., Gordien, K., Brouchet, L., Delisle, M., et al. (2012) · Oncogenesis · doi:10.1038/oncsis.2012.29 · Cited by 124
Self-citationOverexpression of POLQ Confers a Poor Prognosis in Early Breast Cancer Patients
Higgins, G. S., Harris, A. L., Prevo, R., et al. (2010) · Oncotarget · doi:10.18632/oncotarget.124 · Cited by 123
Inagaki, S., Suzuki, T., Ohto, M., Urawa, H., Horiuchi, T., Nakamura, K., & Morikami, A. (2006) · The Plant Cell · doi:10.1105/tpc.105.036798 · Cited by 122
Sharief, F. S., Vojta, P. J., Ropp, P. A., & Copeland, W. C. (1999) · Genomics · doi:10.1006/geno.1999.5843 · Cited by 118
Phenotype-Based Identification of Mouse Chromosome Instability Mutants
Shima, N., Hartford, S. A., Duffy, T., Wilson, L. A., Schimenti, K. J., & Schimenti, J. C. (2003) · Genetics · doi:10.1093/genetics/163.3.1031 · Cited by 115
The translesion DNA polymerase θ plays a dominant role in immunoglobulin gene somatic hypermutation
Zan, H., Shima, N., Xu, Z., Al-Qahtani, A. A., Evinger, A. J., Zhong, Y., Schimenti, J. C., & Casali, P. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600833 · Cited by 115
Rey, L., Sidorova, J. M., Puget, N., Boudsocq, F., Biard, D. S. F., Monnat, R. J., Cazaux, C., & Hoffmann, J. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00115-09 · Cited by 114
Self-citationMasuda, K., Ouchida, R., Takeuchi, A., Saito, T., Koseki, H., Kawamura, K., Tagawa, M., Tokuhisa, T., Azuma, T., & Wang, J. O. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505636102 · Cited by 110
DNA polymerase POLQ and cellular defense against DNA damage
Yousefzadeh, M. J., & Wood, R. D. (2012) · DNA repair · doi:10.1016/j.dnarep.2012.10.004 · Cited by 109
Gilbert, D. M., Takebayashi, S., Ryba, T., Lu, J., Pope, B. D., Wilson, K. A., & Hiratani, I. (2010) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2010.75.011 · Cited by 107
Hogg, M., Seki, M., Wood, R. D., Doublié, S., & Wallace, S. S. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.10.041 · Cited by 106
Prasad, R., Longley, M. J., Sharief, F. S., Hou, E. W., Copeland, W. C., & Wilson, S. H. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp035 · Cited by 103
Ryba, T., Battaglia, D., Chang, B. H., Shirley, J. W., Buckley, Q., Pope, B. D., Devidas, M., Druker, B. J., & Gilbert, D. M. (2012) · Genome Research · doi:10.1101/gr.138511.112 · Cited by 99
DNA polymerase θ (POLQ) can extend from mismatches and from bases opposite a (6-4) photoproduct
Seki, M., & Wood, R. D. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.08.005 · Cited by 89
Goff, J. P., Shields, D. S., Seki, M., Choi, S., Epperly, M. W., Dixon, T. M., Wang, H., Bakkenist, C. J., Dertinger, S. D., Torous, D. K., et al. (2009) · Radiation Research · doi:10.1667/rr1598.1 · Cited by 82
Replication timing, chromosomal bands, and isochores
Costantini, M., & Bernardi, G. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710587105 · Cited by 77
Betous, R., Pillaire, M., Pierini, L., van der Laan, S., Recolin, B., Ohl-Séguy, E., Guo, C., Niimi, N., Grúz, P., Nohmi, T., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.148 · Cited by 76
Self-citationDNA polymerases and somatic hypermutation of immunoglobulin genes
Seki, M., Gearhart, P. J., & Wood, R. D. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400582 · Cited by 71
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
Prioleau, M., Gendron, M., & Hyrien, O. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.10.3536-3549.2003 · Cited by 66
Masuda, K., Ouchida, R., Hikida, M., Kurosaki, T., Yokoi, M., Masutani, C., Seki, M., Wood, R. D., Hanaoka, F., & Wang, J. O. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611849200 · Cited by 65
Clijsters, L., Ogink, J., & Wolthuis, R. M. F. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201211019 · Cited by 61
Hassan‐Zadeh, V., Chilaka, S., Cadoret, J., Ma, K.-W., Boggetto, N., West, A. G., & Prioleau, M. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001277 · Cited by 52
Self-citationInagaki, S., Nakamura, K., & Morikami, A. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000613 · Cited by 52
Pillaire, M., Betous, R., Conti, C., Czaplicki, J., Pasero, P., Bensimon, A., Cazaux, C., & Hoffmann, J. (2007) · Cell Cycle · doi:10.4161/cc.6.4.3857 · Cited by 47
Self-citationDNA Polymerase θ Purified from Human Cells is a High-fidelity Enzyme
Maga, G., Shevelev, I., Ramadan, K., Spadari, S., & Hübscher, U. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00325-x · Cited by 47
Reevaluation of the role of DNA polymerase θ in somatic hypermutation of immunoglobulin genes
Martomo, S. A., Saribasak, H., Yokoi, M., Hanaoka, F., & Gearhart, P. J. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.04.002 · Cited by 45
Hoffmann, J., & Cazaux, C. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.10.001 · Cited by 40
Self-citationIsochores and replication time zones: a perfect match
Schmegner, C., Hameister, H., Vogel, W., et al. (2007) · Cytogenetic and Genome Research · doi:10.1159/000098182 · Cited by 39
Masuda, K., Ouchida, R., Hikida, M., et al. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.06.006 · Cited by 39
Role of DNA polymerase θ in tolerance of endogenous and exogenous DNA damage in mouse B cells
Ukai, A., Maruyama, T., Mochizuki, S., Ouchida, R., Masuda, K., Kawamura, K., Tagawa, M., Kinoshita, K., Sakamoto, A., Tokuhisa, T., et al. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2006.00922.x · Cited by 31
Use of DNA Combing for Studying DNA Replication In Vivo in Yeast and Mammalian Cells
Schwob, É., de Renty, C., Coulon, V., et al. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-815-7_36 · Cited by 29
Asagoshi, K., Lehmann, W., Braithwaite, E. K., Santana‐Santos, L., Prasad, R., Freedman, J. H., Houten, B. V., & Wilson, S. H. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr727 · Cited by 25
Flagged first, then by citations
Cited by
Sorted by citations
Lerner, L. K., Francisco, G., Soltys, D. T., Rocha, C. R. R., Quinet, A., Vessoni, A. T., Castro, L. P., David, T. I. P., Bustos, S. O., Strauss, B. E., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1196 · Cited by 53
Metadata
- Authors
- Fernandez-Vidal, A., Guitton-Sert, L., Cadoret, J.-C., Drac, M., Schwob, E., Baldacci, G., Cazaux, C., & Hoffmann, J.-S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Cazaux, Christophe
- Hoffmann, Jean-Sébastien
- ORCID
- Venue
- Nature Communications
- Published
- 2014-07-03
- Volume
- 5
- Issue
- 1
- Pages
- 4285-4285
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2056093824
- Cited by
- 89
- References
- 66
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 9 · 2022: 9 · 2021: 14 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 12 · 2015: 7 · 2014: 5
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Groupement des Entreprises Françaises dans la lutte contre le Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- DNA polymerase theta, DNA replication timing, replication initiation, origin recognition complex, ORC2, ORC4, MCM proteins, chromatin binding, G1 phase, replication domains, translesion synthesis, DNA repair, human cells
- MeSH terms
- DNA Polymerase theta, Cell Line, Chromatin, DNA-Directed DNA Polymerase, DNA Replication, Humans, G1 Phase, S Phase, Cell Cycle Proteins, Origin Recognition Complex, Minichromosome Maintenance Proteins
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
