Direct involvement of p53 in the base excision repair pathway of the DNA repair machinery

Hagai Offer, Roland Wolkowicz, Devorah Matas, Sara Blumenstein, Zvi Livneh, Varda Rotter

Research output: Contribution to journalArticlepeer-review

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Abstract

The p53 tumor suppressor that plays a central role in the cellular response to genotoxic stress was suggested to be associated with the DNA repair machinery which mostly involves nucleotide excision repair (NER). In the present study we show for the first time that p53 is also directly involved in base excision repair (BER). These experiments were performed with p53 temperature-sensitive (ts) mutants that were previously studied in in vivo experimental models. We report here that p53 ts mutants can also acquire wild-type activity under in vitro conditions. Using ts mutants of murine and human origin, it was observed that cell extracts overexpressing p53 exhibited an augmented BER activity measured in an in vitro assay. Depletion of p53 from the nuclear extracts abolished this enhanced activity. Together, this suggests that p53 is involved in more than one DNA repair pathway. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalFEBS Letters
Volume450
Issue number3
DOIs
StatePublished - 7 May 1999
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by grants from the Israel-USA Binational Science Foundation (BSF) and the German Israeli Foundation for Scientific Research and Development (GIF) (V.R.) and the Israel Cancer Research Fund (to V.R. and Z.L.). V.R. is the incumbent of the Norman and Helen Asher Professorial Chair in Cancer Research at the Weizmann Institute. Z.L. is the incumbent of the Maxwell Ellis Professorial Chair in Biomedical Research.

Keywords

  • Base excision repair
  • DNA repair
  • Temperature-sensitive mutant
  • p53

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