Reduction of DNA damage repair efficiency and accumulation of residual damage following chronic UVB-irradiation of HaCaT cells
Open accessAbstract
Absorption of ultraviolet radiation (UVR) by DNA leads to the predominant formation of cyclobutane pyrimidine dimers (CPD). Since those CPD are responsible for the driver mutations found in skin cancers, their efficient repair is critical. We previously showed that pre-stimulation of fibroblasts with chronic low doses of UVB (CLUV) increases CPD repair efficiency. Since skin cancers are not arising from dermal fibroblasts, this observation is not directly relevant to cutaneous carcinogenesis. We have now exposed HaCaT keratinocytes to a CLUV irradiation protocol to determine whether this pre-stimulation influences CPD removal rate. Similar to fibroblasts, CLUV treatment leads to the accumulation of residual CPD in keratinocytes, which are not repaired but rather tolerated and diluted through DNA replication. In contrast to fibroblasts, in keratinocytes we find that CLUV pre-treatment reduces CPD removal of newly generated damage without inducing a higher sensitivity to UVR-induced cell death. Using our experimental data, we derived a theoretical model to predict CPD induction, dilution and repair that occur in keratinocytes when chronically UVB-irradiated. Altogether, these results suggest that the accumulation of unrepaired CPD and the reduction in repair efficiency caused by chronic UVB exposure might lead to an increase in skin cancer driver mutations.
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
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?
A new study exposed a human keratinocyte cell line to 15 doses of 0.75 standard erythemal doses (SEDs), delivered every 12 h; this chronic low-dose regimen resulted in the accumulation of CPDs that were not repaired.
“A new study exposed a human keratinocyte cell line to 15 doses of 0.75 standard erythemal doses (SEDs), delivered every 12 h; this chronic low-dose regimen resulted in the accumulation of CPDs that were not repaired [260].”
From Environmental consequences of interacting effects of changes in stratospheric ozone, ultraviolet radiation, and climate: UNEP Environmental Effects Assessment Panel, Update 2024 (2025) · cites this paper as [260]
Materials and methods (Cell culture and UVB irradiation; page unavailable) describes 15 irradiations of HaCaT human keratinocytes, every 12 hours, at 75 J/m² UVB per exposure. The Introduction and Conclusion report an accumulation of residual CPDs that were not repaired. The paper does not express the dose as 0.75 standard erythemal doses or establish that equivalence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe chronic low-dose regimen reduced removal of CPDs generated by a single high dose of UV-radiation, without increasing the rate of UV-induced cell death.
“Further, this chronic low-dose regimen reduced removal of CPDs generated by a single high dose of UV-radiation, without increasing the rate of UV-induced cell death.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317 · see citing works
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189 · see citing works
Getting under the skin of epidermal morphogenesis
Fuchs, E., & Raghavan, S. (2002) · Nature Reviews Genetics · doi:10.1038/nrg758 · Cited by 753 · see citing works
Frequent clones of p53-mutated keratinocytes in normal human skin
Jonason, A. S., Kunala, S., Price, G. J., Restifo, R. J., Spinelli, H. M., Persing, J. A., Leffell, D. J., Tarone, R. E., & Brash, D. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.14025 · Cited by 685 · see citing works
Hwang, B. J., Ford, J. M., Hanawalt, P. C., & Chu, G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.2.424 · Cited by 581 · see citing works
Differentiation of the epidermal keratinocyte in cell culture: Formation of the cornified envelope
Sun, T., & Green, H. (1976) · Cell · doi:10.1016/0092-8674(76)90033-7 · Cited by 507 · see citing works
p53 Mutations in human immortalized epithelial cell lines
Lehman, T. A., Modali, R., Boukamp, P., Stanek, J., Bennett, W. P., Welsh, J. A., Metcalf, R. A., Stampfer, M. R., Fusenig, N. E., Rogan, E. M., et al. (1993) · Carcinogenesis · doi:10.1093/carcin/14.5.833 · Cited by 443 · see citing works
Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity
Cleaver, J. E., Lam, E. T., & Revet, I. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2663 · Cited by 428 · cited 1× · see citing works
“Importance of NER for skin cancer prevention is well demonstrated by the fact that a deficiency in NER proteins, such as in xeroderma pigmentosum (XP) patients, leads to an increase of up to 2,000-fold in skin cancer occurrence [9].”
Background<scp>UV</scp> Signature Mutations
Brash, D. E. (2015) · Photochemistry and Photobiology · doi:10.1111/php.12377 · Cited by 401 · see citing works
Molecular mechanisms of UV-induced apoptosis
Kulms, D., & Schwarz, T. (2000) · Photodermatology, Photoimmunology & Photomedicine · doi:10.1034/j.1600-0781.2000.160501.x · Cited by 319 · see citing works
You, Y.-H., Lee, D.-H., Yoon, J.-H., Nakajima, S., Yasui, A., & Pfeifer, G. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107696200 · Cited by 314 · see citing works
Sage, É. (1993) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1993.tb02273.x · Cited by 235 · see citing works
Berg, R. J. W., van Kranen, H. J., Rebel, H. G., de Vries, A., van Vloten, W. A., van Kreijl, C. F., van der Leun, J. C., & de Gruijl, F. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.274 · Cited by 220 · see citing works
Besaratinia, A., Yoon, J., Schroeder, C., Bradforth, S. E., Cockburn, M., & Pfeifer, G. P. (2011) · The FASEB Journal · doi:10.1096/fj.11-187336 · Cited by 155 · cited 2× · see citing works
“Long UVB wavelengths (290–315 nm) are the main wave-lengths responsible for skin cancer initiation and promotion [3, 4].”
BackgroundUltraviolet radiation and skin cancer of humans
Urbach, F. (1997) · Journal of Photochemistry and Photobiology B: Biology · doi:10.1016/s1011-1344(97)00029-8 · Cited by 136 · see citing works
Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair
Rochette, P. J., & Brash, D. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000926 · Cited by 133 · see citing works
Self-citationRegulation of DNA damage recognition and nucleotide excision repair: another role for p53
Ford, J. M. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2005.04.005 · Cited by 117 · see citing works
Rebel, H. G., Mosnier, L. O., Berg, R. J. W., Vries, A. W.-D., STEEG, H. V., van Kranen, H. J., & de Gruijl, F. R. (2001) · PubMed · Cited by 108 · see citing works
Current concept of photocarcinogenesis
Nishisgori, C. (2015) · Photochemical & Photobiological Sciences · doi:10.1039/c5pp00185d · Cited by 102 · see citing works
Therrien, J., Drouin, R., Baril, C., & Drobetsky, E. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15038 · Cited by 92 · see citing works
Molecular mechanisms involved in UV-induced apoptotic cell death
Kulms, D., & Schwarz, T. (2002) · Skin Pharmacology and Physiology · doi:10.1159/000064539 · Cited by 89 · see citing works
Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.
Mitchell, D. L., Greinert, R., de Gruijl, F. R., Guikers, K. L. H., Breitbart, E. W., Byrom, M., Gallmeier, M. M., Lowery, M. G., & Volkmer, B. (1999) · PubMed · Cited by 81 · see citing works
D'Errico, M., Teson, M., Calcagnile, A., Nardo, T., De Luca, N., Lazzari, C., Soddu, S., Zambruno, G., Stefanini, M., & Dogliotti, E. (2005) · Cancer Research · doi:10.1158/0008-5472.432.65.2 · Cited by 64 · see citing works
Apoptosis and efficient repair of DNA damage protect human keratinocytes against UVB
D'Errico, M., Teson, M., Calcagnile, A., De Santis, L. P., Nikaido, O., Botta, E., Zambruno, G., Stefanini, M., & Dogliotti, E. (2003) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401224 · Cited by 62 · see citing works
Induction, repair and accumulation of thymin dimers in the skin of UV-B-irradiated hairless mice
Vink, A. A., Berg, R. J. W., de Gruijl, F. R., Roza, L., & Baan, R. A. (1991) · Carcinogenesis · doi:10.1093/carcin/12.5.861 · Cited by 47 · see citing works
Mallet, J. D., Dorr, M. M., Drigeard Desgarnier, M.-C., Bastien, N., Gendron, S. P., & Rochette, P. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162212 · Cited by 40 · see citing works
Self-citationMitchell, D. L., Byrom, M., Lowery, M. G., Volkmer, B., Breitbart, E. W., & Greinert, R. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01442.x · Cited by 40 · see citing works
Fernandez, T. L., Lonkhuyzen, D. R. V., Dawson, R., Kimlin, M. G., & Upton, Z. (2014) · Photochemistry and Photobiology · doi:10.1111/php.12317 · Cited by 31 · see citing works
Ferguson, B. E., & Oh, D. H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1457 · Cited by 30 · see citing works
Detection of Thymine Dimers in Suprabasal and Basal Cells of Chronically UV-B Exposed Hairless Mice
Vink, A. A., Berg, R. J. W., de Gruijl, F. R., Lohman, P. H. M., Roza, L., & Baan, R. A. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12476606 · Cited by 30 · see citing works
Persistence and Tolerance of DNA Damage Induced by Chronic UVB Irradiation of the Human Genome
Bérubé, R., Desgarnier, M. D., Douki, T., Lechasseur, A., & Rochette, P. J. (2017) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.08.044 · Cited by 29 · see citing works
Self-citationImpaired repair of cyclobutane pyrimidine dimers in human keratinocytes deficient in p53 and p63
Ferguson, B. E., Li, H., Dong, T. K., Hsiao, J. L., & Oh, D. H. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm244 · Cited by 27 · see citing works
Enhancement of UVB-induced DNA damage repair after a chronic low-dose UVB pre-stimulation
Drigeard Desgarnier, M.-C., & Rochette, P. J. (2018) · DNA Repair · doi:10.1016/j.dnarep.2018.01.008 · Cited by 24 · see citing works
Self-citationMitchell, D. L., Byrom, M., Chiarello, S., & Lowery, M. G. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01192.x · Cited by 24 · see citing works
Yegorov, Y. E., & Zelenin, A. V. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00298-9 · Cited by 24 · see citing works
Oh, D. H., & Yeh, K. (2005) · DNA repair · doi:10.1016/j.dnarep.2005.06.004 · Cited by 19 · see citing works
Desgarnier, M. D., Fournier, F., Droit, A., & Rochette, P. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173740 · Cited by 13 · see citing works
Self-citationCourdavault, S., Baudouin, C., Sauvaigo, S., Mouret, S., Candéias, S., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2004) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2004.tb00004.x · Cited by 12 · see citing works
Courdavault, S., Baudouin, C., Sauvaigo, S., et al. (2004) · BioOne Complete (BioOne) · doi:10.1562/0031-8655(2004)079<0145:ucpddn>2.0.co;2 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neale, P. J., Hylander, S., Banaszak, A. T., Häder, D.-P., Rose, K. C., Vione, D., Wängberg, S.-Å., Jansen, M. A. K., Busquets, R., Andersen, M. P. S., et al. (2025) · Photochemical & Photobiological Sciences · doi:10.1007/s43630-025-00687-x · Cited by 32 · see citing works
Elsbroek, L., Reuschlein, K., Karsai, S., Geueke, A., von Petersdorff, M., Bresch, M., Steinkraus, V., Weisenseel, P., Wolf, P., Winnefeld, M., et al. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.11.018 · Cited by 4 · see citing works
Prajapati, G., Patel, S. K., Mourya, D., Sinha, M., Kamar, M. D., Ray, R. S., & Dwivedi, A. (2025) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2025.113227 · Cited by 2 · see citing works
Normal cell responses to 3D-CRT, VMAT, and helical tomotherapy: A comparative study
Phumsankhot, R., Kasetthamrongrat, P., Duangya, A., Watcharawipha, A., Nobnop, W., & Autsavapromporn, N. (2025) · Radiation Medicine and Protection · doi:10.1016/j.radmp.2025.09.002 · Cited by 1 · see citing works
Borges, S. F., Zillmer, J. G. V., Sampaio, A. D., Schwartz, E., & Sampaio, A. L. D. (2024) · Revista Família Ciclos de Vida e Saúde no Contexto Social · doi:10.18554/refacs.v12i4.7393 · Cited by 1 · see citing works
Minerva, P., Arisanty, R., Amelia, R., Intan, S. A., & Wilis, M. (2025) · Tropical Journal of Natural Product Research · doi:10.26538/tjnpr/v9i9.36
- Authors
- Dorr, M. M., & Rochette, P. J.
- Affiliations
- Hôpital du Saint-Sacrement (CA)
- Corresponding author
- Rochette, Patrick J.
- ORCID
- Rochette, Patrick J.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2023-04-07
- Volume
- 18
- Issue
- 4
- Pages
- e0283572
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC10081739
- OpenAlex
- W4362692716
- Cited by
- 6
- References
- 38
- Citations by year
- 2025: 5 · 2024: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- cyclobutane pyrimidine dimers, DNA repair, HaCaT keratinocytes, residual DNA damage, skin cancer, driver mutations, UV-induced cell death, skin carcinogenesis
- MeSH terms
- HaCaT Cells, DNA Damage, DNA Repair, Humans, Pyrimidine Dimers, Skin Neoplasms, Ultraviolet Rays, Keratinocytes
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
