@article{Alaouid2023c,

title = {Aurora A mediated new phosphorylation of RAD51 is observed in Nuclear Speckles},

author = {Mohamad Alaouid and Parfait Kenfack Ymbe and Vanessa Philippot-Ménil and Gwennina Cueff and Alexandre Demeyer and Damien Marquis and Nizar Ayadi and Fabrice Fleury and Houda Benhelli-Mokrani},

url = {http://biorxiv.org/lookup/doi/10.1101/2023.08.11.552966},

doi = {10.1101/2023.08.11.552966},

year  = {2023},

date = {2023-08-12},

urldate = {2023-08-12},

publisher = {openRxiv},

abstract = {To 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 its activity 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 affinity . 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.

},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chabot2019a,

title = {New phosphorylation sites of rad51 by c-met modulates presynaptic filament stability},

author = {Thomas Chabot and Alain Defontaine and Damien Marquis and Axelle Renodon-Corniere and Emmanuelle Courtois and Fabrice Fleury and Yvonnick Cheraud},

doi = {10.3390/cancers11030413},

issn = {20726694},

year  = {2019},

date = {2019-01-01},

journal = {Cancers},

volume = {11},

number = {3},

abstract = {Genomic instability through deregulation of DNA repair pathways can initiate cancer and subsequently result in resistance to chemo and radiotherapy. Understanding these biological mechanisms is therefore essential to overcome cancer. RAD51 is the central protein of the Homologous Recombination (HR) DNA repair pathway, which leads to faithful DNA repair of DSBs. The recombinase activity of RAD51 requires nucleofilament formation and is regulated by post-translational modifications such as phosphorylation. In the last decade, studies have suggested the existence of a relationship between receptor tyrosine kinases (RTK) and Homologous Recombination DNA repair. Among these RTK the c-MET receptor is often overexpressed or constitutively activated in many cancer types and its inhibition induces the decrease of HR. In this study, we show for the first time that c-MET is able to phosphorylate the RAD51 protein. We demonstrate in vitro that c-MET phosphorylates four tyrosine residues localized mainly in the subunit-subunit interface of RAD51. Whereas these post-translational modifications do not affect the presynaptic filament formation, they strengthen its stability against the inhibitor effect of the BRC peptide obtained from BRCA2. Taken together, these results confirm the role of these modifications in the regulation of the BRCA2-RAD51 interaction and underline the importance of c-MET in DNA damage response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Alligand2017,

title = {Functional effects of diphosphomimetic mutations at cAbl-mediated phosphorylation sites on Rad51 recombinase activity},

author = {Brendan Alligand and Magali {Le Breton} and Damien Marquis and François Vallette and Fabrice Fleury},

url = {http://dx.doi.org/10.1016/j.biochi.2017.05.020},

doi = {10.1016/j.biochi.2017.05.020},

issn = {61831638},

year  = {2017},

date = {2017-01-01},

journal = {Biochimie},

volume = {139},

pages = {115--124},

publisher = {Elsevier Ltd},

abstract = {Homologous Recombination enables faithful repair of the deleterious double strand breaks of DNA. This pathway relies on Rad51 to catalyze homologous DNA strand exchange. Rad51 is known to be phosphorylated in a sequential manner on Y315 and then on Y54, but the effect of such phosphorylation on Rad51 function remains poorly understood. We have developed a phosphomimetic model in order to study all the phosphorylation states. With the purified phosphomimetic proteins we performed in vitro assays to determine the activity of Rad51. Here we demonstrate the inhibitory effect of the double phosphomimetic mutant and suggest that it may be due to a defect in nucleofilament formation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}