The DOI matches its Crossref record; 38 of the 40 references it cites were found in a registry or an index.
DDB2 decides cell fate following DNA damage
Open accessAbstract
The xeroderma pigmentosum complementation group E (XP-E) gene product damaged-DNA binding protein 2 (DDB2) plays important roles in nucleotide excision repair (NER). Previously, we showed that DDB2 participates in NER by regulating the level of p21(Waf1/Cip1). Here we show that the p21(Waf1/Cip1) -regulatory function of DDB2 plays a central role in defining the response (apoptosis or arrest) to DNA damage. The DDB2-deficient cells are resistant to apoptosis in response to a variety of DNA-damaging agents, despite activation of p53 and the pro-apoptotic genes. Instead, these cells undergo cell cycle arrest. Also, the DDB2-deficient cells are resistant to E2F1-induced apoptosis. The resistance to apoptosis of the DDB2-deficient cells is caused by an increased accumulation of p21(Waf1/Cip1) after DNA damage. We provide evidence that DDB2 targets p21(Waf1/Cip1) for proteolysis. The resistance to apoptosis in DDB2-deficient cells also involves Mdm2 in a manner that is distinct from the p53-regulatory activity of Mdm2. Our results provide evidence for a new regulatory loop involving the NER protein DDB2, Mdm2, and p21(Waf1/Cip1) that is critical in deciding cell fate (apoptosis or arrest) upon DNA damage.
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In the citing paper
“DDB2 was found to regulate between cell cycle arrest with DDB2 present versus cell cycle arrest when DDB2 is absent through experiments performed in WT and DDB2−/− MEFs [50,51].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [50]
In the citing paper
“Interestingly, they also found that the cell cycle arrest mediator p21Waf1/Cip1 is regulated by DDB2 to induce apoptosis.”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [50]
In the citing paper
“This effect was reversed with silencing Mdm2 in addition to DDB2 in the presence of DNA damage.”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [50]
In the citing paper
“Mdm2 inhibited apoptosis in conjunction with UV, cisplatin and doxorubicin in HeLa cells when DDB2 was silenced [50].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [50]
Citations
Cites
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The codon 72 polymorphic variants of p53 have markedly different apoptotic potential
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UV-Induced Ubiquitylation of XPC Protein Mediated by UV-DDB-Ubiquitin Ligase Complex
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PUMA Couples the Nuclear and Cytoplasmic Proapoptotic Function of p53
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Cazzalini, O., Scovassi, A. I., Savio, M., Stivala, L. A., & Prosperi, E. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.01.009 · Cited by 445
Kang, T.-H., Lindsey-Boltz, L. A., Reardon, J. T., & Sancar, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915085107 · Cited by 250
Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment
van Zyl, B., Tang, D., & Bowden, N. A. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0336 · Cited by 234
Xiao, H., Sun, X., Lin, Z., Yang, Y., Zhang, M., Xu, Z., Liu, P., Liu, Z., & Huang, H. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.023 · Cited by 198
Nucleotide excision repair: Why is it not used to predict response to platinum-based chemotherapy?
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Metadata
- Authors
- Stoyanova, T., Roy, N., Kopanja, D., Bagchi, S., & Raychaudhuri, P.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-06-30
- Volume
- 106
- Issue
- 26
- Pages
- 10690-10695
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2705559
- OpenAlex
- W2034903905
- Cited by
- 108
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 18 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 2 · 2015: 8 · 2014: 7 · 2013: 12 · 2012: 7
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Illinois at Urbana-Champaign
- National Institute on Aging (R01AG024138, AG024138)
- National Cancer Institute (R01CA077637, CA77637)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- DDB2, nucleotide excision repair, p21, apoptosis, cell cycle arrest, MDM2, p53, E2F1, DNA damage response, proteolysis, cell fate determination
- MeSH terms
- Animals, Antineoplastic Agents, Cell Cycle, Cells, Cultured, Cisplatin, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Flow Cytometry, HeLa Cells, Humans, Ultraviolet Rays, Blotting, Western, Aclarubicin, Tumor Suppressor Protein p53, Apoptosis, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, Cyclin-Dependent Kinase Inhibitor p21, Mice, Proto-Oncogene Proteins c-mdm2
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