Identification of new regulations of homologous recombination by O-GlcNAcylation

The "Unité en Sciences Biologiques et Biotechnologies (US2B)" is a research laboratory affiliated with "Nantes Université" and the "Centre national de la recherche scientifique (CNRS UMR 6286)".

The “Mechanism and Regulation of DNA Repair” team, in which the student will be working during their internship, specializes in the modulation of HR by post-translational regulations and the study of synthetic inhibitors targeting RAD51.

Cells are constantly subjected to various stresses that can lead to DNA damage, threatening genome integrity. To counteract this, cells have developed several repair pathways grouped together in an overall process called the DNA damage response (DDR). Double-strand breaks (DSB) are the most threatening for cells and are targeted by homologous recombination (HR). Recently, O-GlcNAcylation, a post-translational modification of glycosylation type, has been shown to be a key factor in DDR. Our team was one of the first to establish the link between O-GlcNAcylation and RDA (Lafont et al. 2020). However, the role of O-GlcNAcylation in RH remains to be elucidated, particularly in the context of cancer, where hyperactive RH can be found, resulting in resistance to anticancer treatment. Our project aims to identify the direct and indirect roles of O-GlcNAcylation on the function of key HR proteins such as RAD51 and BRCA2. To do this, we use a multidisciplinary approach that combines molecular biology, biochemistry, and cell biology. Ultimately, we want to increase our knowledge of HR in order to improve our ability to modulate it with the aim of reducing tumor cell resistance to cancer treatment.

The internship student will be involved in identifying new O-GlcNAcylated HR proteins as well as identifying roles for these O-GlcNAc in the function of these proteins in vitro and in cellulo.

Lafont, Florian, Fabrice Fleury, et Houda Benhelli-Mokrani. 2020. « DNA-PKcs Ser2056 Auto Phosphorylation Is Affected by an O-GlcNAcylation/Phosphorylation Interplay ». Biochimica Et Biophysica Acta. General Subjects 1864 (12): 129705. https://doi.org/10.1016/j.bbagen.2020.129705.

• Master's student

• Skills and knowledge in biochemistry, molecular biology, and cell biology

• Knowledge of glycobiology would be an asset but is not required.

• Laboratory experience (Master's internship or other)

• Interest in fundamental research