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EMBO Rep. 2016 Apr;17(4):508-18. doi: 10.15252/embr.201541181. Epub 2016 Mar 10.

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

Author information

1
Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France.
2
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS UPS, France Equipe labellisée Ligue Nationale Contre le Cancer.
3
Cancer Research Center of Toulouse (CRCT), Inserm UMR 1037 Université Toulouse III-Paul Sabatier, Toulouse, France stefania.millevoi@inserm.fr.

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.

KEYWORDS:

DNA damage; Ku; mRNA translation; p53

PMID:
26964895
PMCID:
PMC4818778
DOI:
10.15252/embr.201541181
[Indexed for MEDLINE]
Free PMC Article

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