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Implication of p53 in base excision DNA repair: in vivo evidence

Oncogene volume 21, pages 731–737 (2002)Cite this article

Abstract

The tumor suppressor p53 plays an important role in response to DNA damage, including DNA repair. One DNA repair pathway, nucleotide excision repair (NER), has been well-documented to be regulated by p53. It seemed probable that p53 may affect other DNA repair pathways. We employed matched isogenic pairs of cell lines, wild-type or p53-deficient, to investigate this question using methyl methanesulfonate (MMS), a base-damaging agent. Alkylation damage induced by MMS is repaired exclusively by the base excision repair (BER) pathway. Cells carrying mutant or no p53 genes exhibited slow BER of MMS-induced DNA damage, and exhibited MMS-sensitivity. One contributing factor is the abundance of DNA polymerase β (β-pol), an enzyme required for BER, which was almost absent in p53 mutant and p53-null cells. Our findings demonstrate an in vivo requirement for p53 in regulating the base excision repair response, a novel finding of great potential importance in understanding the DNA repair branch of the p53 pathway.

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Abbreviations

MMS:

methyl methanesulfonate

BER:

base excision repair

AP:

apurinic site

APE:

apurinic/apyrimidinic endonuclease

β-pol:

DNA-polymerase beta

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Acknowledgements

We thank David W O'Hannesian, Lindsey D Mayo, and two anonymous reviewers for their insightful comments on the manuscript. This work was supported by Indiana University Cancer Center and American Cancer Society grants 1RG84-002 and RSG-02-028-01-CNE (ML Smith).

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Authors and Affiliations

  1. Department of Microbiology, Indiana University Cancer Center, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Young R Seo & Martin L Smith

  2. Walther Cancer Institute, Indianapolis, Indiana, USA

    Young R Seo & Martin L Smith

  3. Department of Biochemistry and Wells Center for Pediatric Oncology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Melissa L Fishel & Mark R Kelley

  4. National Cancer Institute, Bethesda, Maryland, USA

    Sally Amundson

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  1. Young R Seo
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Seo, Y., Fishel, M., Amundson, S. et al. Implication of p53 in base excision DNA repair: in vivo evidence. Oncogene 21, 731–737 (2002). https://doi.org/10.1038/sj.onc.1205129

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