The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.
Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein
Open accessAbstract
The XPA (Xeroderma pigmentosum A) protein is one of the six core factors of the human nucleotide excision repair system. In this study we show that XPA is a rate-limiting factor in all human cell lines tested, including a normal human fibroblast cell line. The level of XPA is controlled at the transcriptional level by the molecular circadian clock and at the post-translational level by a HECT domain family E3 ubiquitin ligase called HERC2. Stabilization of XPA by downregulation of HERC2 moderately enhances excision repair activity. Conversely, downregulation of XPA by siRNA reduces excision repair activity in proportion to the level of XPA. Ubiquitination and proteolysis of XPA are inhibited by DNA damage that promotes tight association of the protein with chromatin and its dissociation from the HERC2 E3 ligase. Finally, in agreement with a recent report, we find that XPA is post-translationally modified by acetylation. However, contrary to the previous claim, we find that in mouse liver only a small fraction of XPA is acetylated and that downregulation of SIRT1 deacetylase in two human cell lines does not affect the overall repair rate. Collectively, the data reveal that XPA is a limiting factor in excision repair and that its level is coordinately regulated by the circadian clock, the ubiquitin-proteasome system and DNA damage.
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“Because of XPA’s crucial functions in NER, the activity of NER and sensitization of cancer cells to chemotherapy can be regulated by transcriptional and post-transcriptional control of the XPA protein [19], [20], [21], [22], [23], [24], [25], [26].”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [21]
In the citing paper
“XPA may serve as a potential target for sensitization to cancer chemotherapy (e.g. cisplatin) via manipulation of available nuclear XPA, either at the transcriptional or post-transcriptional level [53], [54], [55].”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [55]
In the citing paper
“Xeroderma pigmentosum complement group A (XPA), a gene frequently mutated in XP patients, is part of the core incision complex of NER and interacts with DNA as well as many other NER and damage response proteins”
From RETRACTED: PKA-Mediated Phosphorylation of ATR Promotes Recruitment of XPA to UV-Induced DNA Damage (2014) · cites this paper as Kang et al., 2011
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Citations
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
Self-citationNakahata, Y., Kaluzova, M., Grimaldi, B., Sahar, S., Hirayama, J., Chen, D., Guarente, L. P., & Sassone-Corsi, P. (2008) · Cell · doi:10.1016/j.cell.2008.07.002 · Cited by 1,427
SIRT1 regulates circadian clock gene expression through PER2 deacetylation
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Circadian Control of the NAD + Salvage Pathway by CLOCK-SIRT1
Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M., & Sassone-Corsi, P. (2009) · Science · doi:10.1126/science.1170803 · Cited by 1,198
Sancar, A. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.000355 · Cited by 1,131
Self-citationCircadian Clock Feedback Cycle Through NAMPT-Mediated NAD + Biosynthesis
Ramsey, K. M., Yoshino, J., Brace, C. S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.-K., Chong, J. L., Buhr, E. D., Lee, C., et al. (2009) · Science · doi:10.1126/science.1171641 · Cited by 1,126
Physiological functions of the HECT family of ubiquitin ligases
Rotin, D., & Kumar, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2690 · Cited by 1,105
Transcription-coupled DNA repair: two decades of progress and surprises
Hanawalt, P. C., & Spivak, G. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2549 · Cited by 1,081
Differential regulation of mammalian Period genes and circadian rhythmicity by cryptochromes 1 and 2
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Self-citationCircadian Rhythms: Mechanisms and Therapeutic Implications
Levi, F., & Schibler, U. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105208 · Cited by 645
Flagged first, then by citations
1 of the 45 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Boyer, 1991, Cancer Research, 51, 2960
- Cleaver, 1995, Cancer Research, 55, 6152
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Items 101–124 of 124
Pradhan, S., & Mattaparthi, V. S. K. (2017) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2017.1388285 · Cited by 3
Introduction to Mammalian Circadian Clock System
Zhao, M., Lu, D., Chen, M., & Wu, B. (2020) · Springer eBooks · doi:10.1007/978-981-15-8807-5_1 · Cited by 4
(2013) · Digital Commons - East Tennessee State University (East Tennessee State University) · Cited by 3
Gao, X., Tang, M., Tian, S., Li, J., Wei, S., Hua, S., & Liu, W. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296829 · Cited by 3
Améndola-Pimenta, M., Alcocer-Domínguez, J. C., Sandoval-Gío, J. J., González-Penagos, C. E., Zamora‐Briseño, J. A., Ek-Huchim, J. P., & Rodríguez‐Canul, R. (2021) · Bulletin of Environmental Contamination and Toxicology · doi:10.1007/s00128-021-03272-x · Cited by 3
Biochemistry That Times the Day
Egli, M., & Johnson, C. H. (2014) · Biochemistry · doi:10.1021/bi5014968 · Cited by 3
Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma
Gao, X., Tang, M., Tian, S., Li, J., & Liu, W. (2021) · PeerJ · doi:10.7717/peerj.11733 · Cited by 2
Bănescu, C. V., Duicu, C., & Dobreanu, M. (2011) · InTech eBooks · doi:10.5772/26145 · Cited by 1
Characterization of the multifunctional XPG protein during Nucleotide-excision-repair
Schubert, S. (2014) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-4515 · Cited by 2
Illuminating genome repair by photolyase
Laughery, M. F., & Wyrick, J. J. (2025) · Photochemistry and Photobiology · doi:10.1111/php.70047 · Cited by 1
Retraction: AKAP12 mediates PKA-induced phosphorylation of ATR to enhance nucleotide excision repair
Jarrett, S. G., Horrell, E. M. W., & D'Orazio, J. A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa984 · Cited by 1
RetractedBeardmore, R. (2015) · Bangor University Research Portal (Bangor University)
Jarrett, S. G., Carter, K. M., Shelton, B. J., & D'Orazio, J. A. (2021) · Scientific Reports · doi:10.1038/s41598-020-80467-y
RetractedDNA Damage, Repair, and Advanced DNA Damage Detection Technologies
Hernandez, A., Goel, K., Hussain, S., & Gassman, N. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00179-0 · Cited by 1
Demenge, A., Lim, J., Roc, A., Zámbó, B., Gógl, G., Cousido-Siah, A., McEwen, A. G., Bonhoure, A., Kostmann, C., Fagotto‐Kaufmann, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.16.670041
RNAi and Chemical-Based High Content Screening for the Normalization of XPC Phenotyope
Kobaisi, F. (2021) · theses.fr (ABES) · doi:10.70675/e34b8c43z081az4c41zad64z8e0c753e5c20
The circadian architecture of tumor immunity: mechanistic insights and treatment strategies
Wang, H. Y., Guo, B., Li, D., Liu, Y., Cheng, K., Zhang, W., & Liang, H. (2026) · Biomarker Research · doi:10.1186/s40364-026-00972-6
Genomic Stress and DNA Repair During Macrophage Differentiation and Inflammatory Activation
Jo, S.-G., Jeon, J., Jeon, Y.-J., Park, S.-J., & Kang, T. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188276
Self-citationXPA lactylation is required for UV-induced DNA damage repair
Yang, J., Ding, X., Zeng, Z., Yin, H., He, Y., Jin, M., Huang, B., Wang, Z., Yang, X., Li, R., et al. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag947
Metadata
- Authors
- Kang, T.-H., Reardon, J. T., & Sancar, A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Sancar, A.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-30
- Volume
- 39
- Issue
- 8
- Pages
- 3176-3187
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3082913
- OpenAlex
- W2116594363
- Cited by
- 124
- References
- 45
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 15 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 13 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 7 · 2012: 11
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM032833, R01GM031082, GM310.82, R37GM031082, GM32833)
- National Institute of Environmental Health Sciences (P30ES010126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- XPA, nucleotide excision repair, xeroderma pigmentosum, HERC2, E3 ubiquitin ligase, ubiquitination, protein stability, circadian clock, SIRT1, protein acetylation, DNA damage response, chromatin association, transcriptional regulation, post-transcriptional regulation, mouse liver
- MeSH terms
- Acetylation, Animals, Cell Line, DNA Damage, DNA Repair, Fibroblasts, Humans, Transcription, Genetic, Ubiquitin-Protein Ligases, Mice, Xeroderma Pigmentosum Group A Protein, Ubiquitination, Circadian Clocks
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