1,721,019 research outputs found
The cyclin-dependent kinase inhibitor p21(CDKN1A) as target of anti-cancer drugs
Full text linkp21(CDKN1A) (WAF1/CIP1/SDI1), the cyclin-dependent kinase (CDK) inhibitor belonging to the Cip/Kip family, was first described as a potent inhibitor of cell proliferation and DNA replication, both in physiological conditions and after DNA damage. More recently, p21 has been recognized to play additional and fundamental roles in other important pathways, including regulation of transcription, apoptosis and DNA repair. Knock-out mouse studies combined with biochemical and functional analysis of cells in culture have indicated a tumor suppressor activity for p21. However, these lines of evidence have been complicated by other findings indicating that p21 can exhibit oncogenic properties. In fact, the evidence that p21 expression may lead to proliferation arrest, is counterbalanced by the rescue of tumor cells from drug-induced apoptosis, and by promoting a metastatic potential. For these reasons, p21 is considered a protein with a dual behavior, with potential benefits, as well as dangerous effects of its expression in malignant cells. Thus, the effectiveness of targeting p21 expression for antitumor therapy needs to be carefully evaluated accordingly. This review summarizes the functions and regulations of p21, and focuses on its involvement in human diseases (particularly cancer), and on the pharmacological approaches to target p21 expression (either positively or negatively) for anticancer therapy. Based on these approaches, the search for new molecules able to promote the tumor-suppressor activity, and/or to interfere with the oncogenic properties of p21, could be promising
UV-induced PCNA complex formation in nucleotide excision repair detective human fibroblasts
No full textDNA damage accumulation and efficiency of DNA repair process in Down syndrome cell model systems
No full textUltrastructure and cytochemistry of circulating erythrocytes during the annual cycle of Rana esculenta L.
No full textAn improved method for the detection of nucleotide excision repair factors at local UV DNA damage sites.
No full textAmong different DNA repair processes that cells use to face with DNA damage, nucleotide excision repair (NER) is particularly important for the removal of a high variety of lesions, including those generated by some antitumor drugs. A number of factors participating in NER, such as the TFIIH complex and the endonuclease XPG are also involved in basal processes, e.g. transcription. For this reason, localization of these factors at DNA damage sites may be difficult. Here we have applied a mild digestion of chromatin with DNase I to improve the in situ extraction necessary to detect chromatin-bound proteins by immunofluorescence. We have compared this method with different extraction protocols and investigated its application on different cell types, and with different antibodies. Our results show that a short DNase I treatment before the immunoreaction, enhances the fluorescence signal of NER proteins, such as XPG, DDB2 and XPC. In addition, our findings indicate that the antibody choice is a critical factor for accurate localization of DNA repair proteins at DNA damage sites. In conclusion, a mild DNA digestion with DNase I improves the immunofluorescence detection of the recruitment of NER factors at local DNA damage sites by enhancing accessibility to the antibodies, independently of the cell type
Ruolo della proteina p21waf1/cip1 nella risposta cellulare al danno al DNA indotto da radiazioni UVC
No full textExploring the interactions between DDB2 and proteins involved in DNA nucleodite excision repair
No full textFibroblasti umani p21CDKN1-null che esprimono hTERT sono più sensibili alla radiazione UVC e mostrano una riduzione del reclutamento di PCNA, XPG e CAF1 ai siti di riparazione del DNA
No full textPCNA is normally recruited at repair sites in p21waf1/cip1-deficient human fibroblasts showing reduced efficiency in nucleotide excision repair
No full textExpression of p21CDNK1A does not affect PCNA-dependent nucleotide excision repair in human cells
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