Implication of p53 in base excision dna repair: In vivo evidence

Young R. Seo, Melissa Fishel, Sally Amundsen, Mark Kelley, Martin L. Smith

Research output: Contribution to journalArticle

93 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)731-737
Number of pages7
JournalOncogene
Volume21
Issue number5
DOIs
StatePublished - Jan 24 2002

Keywords

  • DNA-repair
  • p53
  • Polymerase-beta

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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