ArticleThe Journal of biological chemistry2011
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein-dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor protein p21Waf1/Cip1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Revisiting the Function of p21International journal of molecular sciences · 2022Review
- Anti-tumor immunity in mismatch repair-deficient colorectal cancers requires type I IFN-driven CCL5 and CXCL10.The Journal of experimental medicine · 2021Article
- A comprehensive in vivo and mathematic modeling-based kinetic characterization for aspirin-induced chemoprevention in colorectal cancer.Carcinogenesis · 2020Article
- Cancer stem cell-associated miRNAs serve as prognostic biomarkers in colorectal cancer.JCI insight · 2019Article
- Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer.Scientific reports · 2018Article
- Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression.Carcinogenesis · 2017Article
- Mismatch repair regulates Cdt1 after UV damage.Cell cycle (Georgetown, Tex.) · 2017Article
- Mismatch repair proteins recruited to ultraviolet light-damaged sites lead to degradation of licensing factor Cdt1 in the G1 phase.Cell cycle (Georgetown, Tex.) · 2017Article
- Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer.Oncotarget · 2016Article
- Novel Evidence for Curcumin and Boswellic Acid-Induced Chemoprevention through Regulation of miR-34a and miR-27a in Colorectal Cancer.Cancer prevention research (Philadelphia, Pa.) · 2015Article
- Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer.Carcinogenesis · 2015Article
- Mitotic UV irradiation induces a DNA replication-licensing defect that potentiates G1 arrest response.PloS one · 2015Article
- Article
- A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase δ in response to DNA damage and during the S phase.The Journal of biological chemistry · 2013Article
- A simple and reproducible breast cancer prognostic test.BMC genomics · 2013Article
- Major differences between tumor and normal human cell fates after exposure to chemotherapeutic monofunctional alkylator.PloS one · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
p21(Waf1/Cip1) protein levels respond to DNA damage; p21 is induced after ionizing radiation, but degraded after UV. p21 degradation after UV is necessary for optimal DNA repair, presumably because p21 inhibits nucleotide excision repair by blocking proliferating cell nuclear antigen (PCNA). Because p21 also inhibits DNA mismatch repair (MMR), we investigated how p21 levels respond to DNA alkylation by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which triggers the MMR system. We show that MNNG caused rapid degradation of p21, and this involved the ubiquitin ligase Cdt2 and the proteasome. p21 degradation further required MSH2 but not MLH1. p21 mutants that cannot bind PCNA or cannot be ubiquitinated were resistant to MNNG. MNNG induced the formation of PCNA complexes with MSH6 and Cdt2. Finally, when p21 degradation was blocked, MNNG treatment resulted in reduced recruitment of MMR proteins to chromatin. This study describes a novel pathway that removes p21 to allow cells to efficiently activate the MMR system.
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