The dual role model for p53 in maintaining genomic

Authors: F Janus N Albrechtsen I Dornreiter L Wiesmüller F Grosse W Deppert

Publish Date: 2014/02/06

Volume: 55, Issue: 1, Pages: 12-27

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Abstract

The tumour suppressor p53 is a potent mediator of cellular responses against genotoxic insults In this review we describe the multiple functions of p53 in response to DNA damage with an emphasis on p53s role in DNA repair We summarize data demonstrating that p53 actively participates in various processes of DNA repair and DNA recombination via its ability to interact with components of the repair and recombination machinery and by its various biochemical activities An important aspect in evaluating p53 functions is provided by the finding that the core domain of p53 harbours two mutually exclusive biochemical activities sequencespecific DNA binding required for its transactivation function and 3′–5′ exonuclease activity possibly involved in aspects of DNA repair Based on the finding that modifications of p53 which lead to activation of its sequencespecific DNAbinding activity result in inactivation of its 3′–5′ exonuclease activity we propose that p53 exerts its functions as a ‘guardian of the genome’ at various levels in its noninduced state p53 should not be regarded as a ‘dead’ protein but for example via its exonuclease activity might be actively involved in prevention and repair of endogenous DNA damage Upon induction through exogenous DNA damage p53 will exert its welldocumented functions as a superior response element in various types of cellular stress This dual role model for p53 in maintaining genomic integrity significantly enhances p53s possibilities as a guardian of the genome

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