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Titolo:
PERSISTENT DNA-DAMAGE INDUCED BY ULTRAVIOLET-LIGHT INHIBITS P21(WAF1)AND BAX EXPRESSION - IMPLICATIONS FOR DNA-REPAIR, UV SENSITIVITY AND THE INDUCTION OF APOPTOSIS
Autore:
MCKAY BC; LJUNGMAN M; RAINBOW AJ;
Indirizzi:
MCMASTER UNIV,DEPT BIOL LIFE SCI,BLDG 218A,1280 MAIN ST W HAMILTON ONL8S 4K1 CANADA MCMASTER UNIV,DEPT BIOL HAMILTON ON L8S 4K1 CANADA UNIV MICHIGAN,CTR COMPREHENS CANC,DIV CANC BIOL,DEPT RADIAT ONCOL ANNARBOR MI 48109
Titolo Testata:
Oncogene
fascicolo: 5, volume: 17, anno: 1998,
pagine: 545 - 555
SICI:
0950-9232(1998)17:5<545:PDIBUI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSCRIPTION-COUPLED REPAIR; CYCLIN-DEPENDENT KINASES; LI-FRAUMENI SYNDROME; PIGMENTOSUM GROUP-C; LARGE T-ANTIGEN; CELL-CYCLE; XERODERMA-PIGMENTOSUM; EXCISION-REPAIR; G(1) ARREST; P53-DEPENDENT APOPTOSIS;
Keywords:
APOPTOSIS; DNA REPAIR; E2F-1; E2F-4; VIRAL TUMOR ANTIGENS; P21(WAF1);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
73
Recensione:
Indirizzi per estratti:
Citazione:
B.C. Mckay et al., "PERSISTENT DNA-DAMAGE INDUCED BY ULTRAVIOLET-LIGHT INHIBITS P21(WAF1)AND BAX EXPRESSION - IMPLICATIONS FOR DNA-REPAIR, UV SENSITIVITY AND THE INDUCTION OF APOPTOSIS", Oncogene, 17(5), 1998, pp. 545-555

Abstract

Ultraviolet light (UV) induced DNA lesions efficiently block transcript elongation and induce the p53 response. Although p53 contributes totranscriptional activation of the p21(WAF1) and bar genes, accumulation of these proteins requires that these genes are free of UV induced pyrimidine dimers, We assessed the level of expression of p53 and the p53 regulated p21(WAF1) and bar gene products in normal diploid fibroblasts (NDF) and several nucleotide excision repair deficient fibroblasts following UV-irradiation, At low UV fluences, increased expression of p53, p21(WAF1) and bar was only observed in fibroblasts deficient in transcription coupled repair (TCR), Whereas p53 protein levels increased in all cell types at high UV fluences, p21(WAF1) levels initiallydecreased and then recovered in a manner dependent on TCR, At later times, expression of p21(WAF1) and bar was only elevated in TCR-proficient cells. The lack of TCR strongly correlated with an enhanced induction of apoptosis, Furthermore, we assessed the effect of modulation ofthe p53/p21(WAF1)/pRb pathway on clonogenic survival following UV irradiation. Expression of E2F-1, E2F-4, and the large tumour antigens ofSV40 and Polyomavirus conferred UV sensitivity to NDF whereas p21(WAF1) protected cells against UV treatment, We propose that the fluence dependent attenuation of protective functions of p53 by blockage of transcription favours apoptosis following UV exposure.

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Documento generato il 30/11/20 alle ore 06:58:57