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Role of p53 in Double-Strand Break Repair

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Genome Integrity

Part of the book series: Genome Dynamics and Stability ((GENOME,volume 1))

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Abstract

In addition to p53's classical tumour suppressor functions in cell cycle control and apoptosis induction, p53 exhibits direct regulatory activities in double-strand break repair. In this review, we summarize data from biochemical, cell based and in vivo approaches demonstrating that wild-type p53 restrains excessive and mutagenic DNA exchange events. Thus, p53 appears to exhibit fidelity control of homologous recombination, and recent evidence also suggests that p53 counteracts error-prone non-homologous end-joining. Additionally, we discuss a novel role for p53: stimulation of recombination via pathways involving topoisomerase I and/or sequence-specific DNA binding. In summary, p53 either functions as a global suppressor of mutagenic genome rearrangements or contributes to recombinative repair, when it is recruited to specific repair complexes by molecular interactions with topoisomerase I and/or other binding partners. The p53 protein therefore combines two genetically separable regulatory functions in recombinative DNA repair that may have implications for a loss-of-function versus gain-of-function phenotype of p53 mutants in genetic destabilization.

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Authors and Affiliations

  1. Universitätsklinik für Kinder und Jugendmedizin, Eythstr. 24, 89075, Ulm, Germany

    Susanne Andrea Gatz

  2. Universitätsfrauenklinik, Prittwitzstr. 43, 89075, Ulm, Germany

    Lisa Wiesmüller

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  1. Susanne Andrea Gatz
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  2. Lisa Wiesmüller
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Correspondence to Lisa Wiesmüller .

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Dirk-Henner Lankenau

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© 2005 Springer-Verlag Berlin Heidelberg

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Gatz, S.A., Wiesmüller, L. (2005). Role of p53 in Double-Strand Break Repair. In: Lankenau, DH. (eds) Genome Integrity. Genome Dynamics and Stability, vol 1. Springer, Berlin, Heidelberg . https://doi.org/10.1007/7050_009

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