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A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function
Author(s) -
Lamaa Assala,
Le Bras Morgane,
Skuli Nicolas,
Britton Sébastien,
Frit Philippe,
Calsou Patrick,
Prats Hervé,
Cammas Anne,
Millevoi Stefania
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201541181
Subject(s) - function (biology) , cancer , library science , biology , computer science , genetics
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.