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A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function.

ABSTRACT: Ku heterodimer is a DNA binding protein with a prominent role in DNA repair. Here, we investigate whether and how Ku impacts the DNA damage response by acting as a post-transcriptional regulator of gene expression. We show that Ku represses p53 protein synthesis and p53-mediated apoptosis by binding to a bulged stem-loop structure within the p53 5' UTR However, Ku-mediated translational repression of the p53 mRNA is relieved after genotoxic stress. The underlying mechanism involves Ku acetylation which disrupts Ku-p53 mRNA interactions. These results suggest that Ku-mediated repression of p53 mRNA translation constitutes a novel mechanism linking DNA repair and mRNA translation.

SUBMITTER: Lamaa A

PROVIDER: S-EPMC4818778 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function.

Lamaa Assala A Le Bras Morgane M Skuli Nicolas N Britton Sébastien S Frit Philippe P Calsou Patrick P Prats Hervé H Cammas Anne A Millevoi Stefania S

EMBO reports 20160310 4

Ku heterodimer is a DNA binding protein with a prominent role in DNA repair. Here, we investigate whether and how Ku impacts the DNA damage response by acting as a post-transcriptional regulator of gene expression. We show that Ku represses p53 protein synthesis and p53-mediated apoptosis by binding to a bulged stem-loop structure within the p53 5' UTR However, Ku-mediated translational repression of the p53 mRNA is relieved after genotoxic stress. The underlying mechanism involves Ku acetylatio ...[more]

PMID: 26964895

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