p53 in recombination and repair.
Convergent studies demonstrated that p53 regulates homologous recombination (HR) independently of its classic tumour-suppressor functions in transcriptionally transactivating cellular target genes that are implicated in growth control and apoptosis. In this review, we summarise the analyses of the involvement of p53 in spontaneous and double-strand break (DSB)-triggered HR and in alternative DSB repair routes. Molecular characterisation indicated that p53 controls the fidelity of Rad51-dependent HR and represses aberrant processing of replication forks after stalling at unrepaired DNA lesions. These findings established a genome stabilising role of p53 in counteracting error-prone DSB repair. However, recent work has also unveiled a stimulatory role for p53 in topoisomerase I-induced recombinative repair events that may have implications for a gain-of-function phenotype of cancer-related p53 mutants. Additional evidence will be discussed which suggests that p53 and/or p53-regulated gene products also contribute to nucleotide excision, base excision, and mismatch repair.
Universitätsklinik für Kinder- und Jugendmedizin, Eythstr. 24, 89075 Ulm, Germany.
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Gatz
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Wiesmüller
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; D045643:DNA Repair Enzymes