p53: traffic cop at the crossroads of DNA repair and recombination

Abstract

The transcription-independent function of p53 facilitates DNA repair and controls recombination. p53 modulates nucleotide-excision repair (NER) by transactivating repair-specific genes p48^DDB2 and xeroderma pigmentosum complementation group C (XPC); p48^DDB2 is involved in the transportation of XPC to the sites of DNA damage. p53 also influences the activities of XPB and XPD helicases, and possibly functions as a chromatin-accessibility factor. p53 facilitates base-excision repair (BER) mainly via association with BER components. For example, the in vivo interaction of p53 with APE1/REF1 and DNA polymerase β enhances BER. p53 can regulate mismatch repair (MMR) by transactivating the MSH2 gene and forming multi-functional complexes involving repair-specific (MSH2 and MSH6) and recombination (such as RAD50 and RAD51) proteins. Wild-type p53 protein might inhibit error-prone, but not error-free, NHEJ. p53 can control homologous recombination (HR) in vitro by specific recognition of the heteroduplex intermediates, and in vivo by modulating the functions of different HR-specific proteins. RecQ-family helicases and p53 have functional inter-regulatory relationships during HR. For example, the Bloom's syndrome (BLM) helicase enhances p53 accumulation at the sites of stalled replication forks in vivo.