A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such as p21WAF1, BAX, and PUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage. 1. Introduction The initial chromatin-associated molecular event upon DNA damage is the activated ataxia telangiectasia mutated- (ATM-) mediated phosphorylation of histone variant H2AX (γH2AX), which marks the sites of DNA damage (nuclear foci) [1]. Then a large nuclear adaptor protein termed mediator of DNA damage response 1 (MDC1)/nuclear factor with BRCT domain 1(NFBD1) associates with the sites of DNA damage and facilitates the recruitment of DNA repair machinery including MRN (MRE11, Rad50, and NBS1) complex onto nuclear foci to repair damaged DNA [2–5]. When cells receive the repairable DNA damage, cell cycle arrest takes place to save time to correctly repair damaged DNA, and then cells with repaired DNA reenter into the normal cell cycle (cell survival). In contrast, when cells receive the severer DNA damage, which cannot be repaired, cells with seriously damaged DNA undergo apoptotic cell death and are then eliminated from tissues (cell death). Thus, the appropriate DNA damage response plays an important role to maintain genomic integrity to avoid genomic aberrations such as deletions and mutations, which result in genomic instability and finally induce tumor formation [6–8]. p53 has been initially identified as a 53？KDa of nuclear protein which tightly associated with oncogenic simian virus 40
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