p53 in the DNA-Damage-Repair Process

Abstract

The cells in the human body are continuously challenged by a variety of genotoxic attacks. Erroneous repair of the DNA can lead to mutations and chromosomal aberrations that can alter the functions of tumor suppressor genes or oncogenes, thus causing cancer development. As a central tumor suppressor, p53 guards the genome by orchestrating a variety of DNA-damage-response (DDR) mechanisms. Already early in metazoan evolution, p53 started controlling the apoptotic demise of genomically compromised cells. p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems. It thus appears as if p53 is multitasking in providing protection from cancer development by maintaining genome stability.

Figure 1.

Examples of p53 interactions with DNA-repair pathways. (A–C) Simplified representations of canonical DNA-repair pathways: nucleotide excision repair (NER), base excision repair (BER), and mismatch repair (MMR). Factors with transcription-related interactions are highlighted in orange and factors with nontranscriptional interactions are highlighted in blue. Note that OGG1 has both transcription-dependent and -independent interactions with p53 during base excision repair. Red arrows indicate regulatory effects on p53.

Figure 2.

Examples of p53 interactions with double-strand break repair pathways (left) and p53 checkpoint signaling (right). (A,B) Simplified representations of double-strand break repair via homologous recombination (HR) and nonhomologous end joining (NHEJ). (C) Simplified representation of p53 signaling at double-strand breaks. Factors with transcription-related interactions are highlighted in orange and factors with nontranscriptional interactions are highlighted in blue. Note that RAD51 has both transcription-dependent and -independent interactions with p53 during base excision repair. Red labels and red arrows indicate regulatory effects on p53.