Journal Article

PolyADP-ribose-mediated regulation of p53 complexed with topoisomerase I following ionizing radiation

Heather M. Smith and Andrew J. Grosovsky

in Carcinogenesis

Volume 20, issue 8, pages 1439-1444
Published in print August 1999 | ISSN: 0143-3334
Published online August 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.8.1439
PolyADP-ribose-mediated regulation of p53 complexed with topoisomerase I following ionizing radiation

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This investigation demonstrates that the p53 and topoisomerase I (topo I) proteins which form a molecular complex in vivo are polyADP ribosylated following 1 Gy of γ irradiation. Immunoprecipitations using a topo I monoclonal antibody were performed on protein extracts from γ-irradiated TK6 human lymphoblastoid cells. Western blots on topo I immunoprecipitations probed with a polyADP-ribose polymer antibody demonstrated that several proteins, including p53, are co-immunoprecipitated with topo I. Furthermore, p53 and topo I are ADP ribosylated within 15 min following γ irradiation. Unlike the other proteins within the complex, p53 is polyADP ribosylated at low levels in non-irradiated cells, and it is also the most heavily polyADP ribosylated following irradiation. Radiation induced polyADP ribosylation persists for at least 48 h following exposure. The DNA damage response does not involve the recruitment of free p53 to complex with topo I; the amount of p53 protein complexed with topo I was found to be independent of radiation exposure. It has recently been reported that p53 acts to catalytically stimulate the activity of topo I in the absence of DNA damage. We hypothesize that the rapid modification of the complex by polyADP ribosylation following radiation is a regulatory response to diminish topo I cleavage in the presence of DNA damage.

Keywords: PARP, polyADP-ribose polymerase; topo I, topoisomerase I

Journal Article.  3929 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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