Aurora A mediated new phosphorylation of RAD51 is observed in Nuclear Speckles

Abstract

ABSTRACTTo maintain its genome integrity, the cell uses complementary and orchestrated processes, among which is the DNA Damage Response. Pre mRNA maturation is an essential step of the DNA damage response that provides an adapted proteome in order to face genotoxic stress. We describe here a new phosphorylation of the RAD51 recombinase, on its Ser97 residue. This new Aurora A mediated RAD51 phosphorylation modulates itsin vitroactivity evaluated by D-loop and polymerization assays. Using recombinant proteins, we show that RAD51 is an RNA binding protein and that the Ser97 phosphorylation modulates its RNA binding affinityin vitro. Using a specifically generated antibody we revealed that this Ser97 phosphorylation is correlated with RAD51 localization into the RNA maturation membrane less organelles, Nuclear Speckles. We describe here for the first time the presence of RAD51 DNA repair factor within the Nuclear Speckles, raising the hypothesis of a possible role for RAD51 in splicing modulation. This point is of particular interest in the context of splicing profiles modulations associated with radio and/or chemoresistance.