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Structural and functional involvement of p53 in BER in vitro and in vivo

Oncogene volume 20, pages 581–589 (2001)Cite this article

Abstract

p53 is involved in several DNA repair pathways. Some of these require the specific transactivation of p53-dependent genes and others involve direct interactions between the p53 protein and DNA repair associated proteins. Previously, we have shown that p53 acts directly in Base Excision Repair (BER) when assayed under in vitro conditions. Our present data indicate that this involvement is independent of the transcriptional activity of the p53 molecule. We found that under both in vitro and in vivo conditions, a p53 transactivation-deficient molecule, p53-22-23 was more efficient in BER activity than was wild type p53. However, mutations in the core domain or C-terminal alterations strongly reduced p53-mediated BER activity. These results are consistent with the hypothesis that the involvement of p53 in BER activity, a housekeeping DNA repair pathway, is a prompt and immediate one that does not involve the activation of p53 transactivation-dependent mechanisms, but rather concerns with the p53 protein itself. In an endogenous DNA damage status p53 is active in BER pathways as a protein and not as a transcription factor.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Hagai Offer, Michael Milyavsky, Neta Erez, Devorah Matas, Irit Zurer & Varda Rotter

  2. Laboratory of Human Carcinogenesis NCI-NIH Bethesda, Maryland, MD 20896, USA

    Curtis C Harris

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  1. Hagai Offer
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  2. Michael Milyavsky
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  7. Varda Rotter
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Offer, H., Milyavsky, M., Erez, N. et al. Structural and functional involvement of p53 in BER in vitro and in vivo. Oncogene 20, 581–589 (2001). https://doi.org/10.1038/sj.onc.1204120

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