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Review
. 2016 Jun 1;6(6):a026096.
doi: 10.1101/cshperspect.a026096.

Genome Stability Requires p53

Christine M Eischen  1
Affiliations
Review

Genome Stability Requires p53

Christine M Eischen. Cold Spring Harb Perspect Med. .

Abstract

It is now clear that functional p53 is critical to protect the genome from alterations that lead to tumorigenesis. However, with the myriad of cellular stresses and pathways linked to p53 activation, much remains unknown about how p53 maintains genome stability and the proteins involved. The current understanding of the multiple ways p53 contributes to genome stability and how two of its negative regulators, Mdm2 and Mdmx, induce genome instability will be described.

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Figures

Figure 1.
Figure 1.
p53 activation and the upstream regulators and downstream effectors. p53 is activated by hyperproliferation through Arf activation and DNA-damage signaling through modulation of Mdm2 and activation of the DNA-damaged ataxia-telangiectasia mutated (ATM) and/or ATM- and RAD3-related (ATR) kinase. Activation of p53 induces the transcriptional up-regulation of one or more target genes that mediate one of the biological effects indicated. A cell-cycle arrest caused by checkpoint activation and DNA damage that is not repairable can ultimately induce apoptosis. MRN, Mre11/Rad50/Nbs1.
Figure 2.
Figure 2.
p53 inhibits, whereas Mdm2/Mdmx and aging induce, genome instability. Various forms of genome instability (listed in the center) can lead to increased cellular transformation potential and the other outcomes on the right. The role of p53, Mdm2/Mdmx, and aging are indicated.
See this image and copyright information in PMC

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