PMID: 9421152Jan 8, 1998Paper

The response of proliferating cell nuclear antigen to ionizing radiation in human lymphoblastoid cell lines is dependent on p53

Radiation Research
F WenzJ B Little

Abstract

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein for DNA polymerase delta and epsilon involved in DNA replication and nucleotide excision repair. There are two intranuclear fractions: a detergent-extractable, soluble fraction and a tightly DNA-bound fraction. To function, PCNA forms a trimeric sliding clamp which is loaded onto DNA. To better understand the role of the p53/p21 pathway in the regulation of PCNA after irradiation, we studied three closely related human lymphoblastoid cell lines, WTK1, TK6 and TK6E6, an HPV16 E6-transfected line, that differ in p53 status, radiosensitivity and susceptibility to radiation-induced apoptosis. Time-dependent changes in PCNA levels were measured in the different nuclear fractions by Western blot analysis after protein crosslinking. The results were compared to those for human diploid fibroblasts studied under different growth conditions. There was no change in total cellular levels of PCNA after irradiation, consistent with predominantly post-translational regulation. Changes in intranuclear distribution and complex formation occurred in a p53/p21-dependent manner. The loading of PCNA onto DNA was increased in cells with low p21 levels. A disruption of PCNA trimers was...Continue Reading

Citations

Dec 21, 2004·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Mustasim N RumiVincent D Pellegrini
Sep 17, 2002·American Journal of Respiratory and Critical Care Medicine·Sushmita GhoshGilbert F Morris
Sep 13, 2006·International Seminars in Surgical Oncology : ISSO·M TahirP Whitford
Aug 30, 2014·PloS One·Guillaume VaresTetsuo Nakajima

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