Dr. Jean-Baptiste Charbonnier - Ku70/80 acts as the main hub of the c-NHEJ pathway

Jean-Baptiste Charbonnier

Institute of Integrated Biology of the Cell, Gif-sur-Yvette

Ku70/80 acts as the main hub of the c-NHEJ pathway

An important axis in radiobiology is to combine radiation therapy with inhibitors of the DNA repair pathways to increase radio-sensitivity and overcome radiation resistance of some cancer cells. Our objectives is to unveil the molecular mechanism of the NHEJ (Non Homologous End Joining) pathway and to characterize new specific inhibitors of this pathway. Ku70/Ku80 heterodimer (Ku) is a central player of the NHEJ for DSB recognition and in downstream DNA events (processing and ligation steps). We showed these last years tthat Ku can recruit several enzymes of the NHEJ pathway through direct interactions in particular through Ku Binding Motifs (KBM) present on its partners. It thus acts as a central hub that coordinates the whole NHEJ. ​​​​

Selected publications

• Nemoz C, Ropars V, Frit P, Gontier A, Drevet P, Yu J, Guerois R, Pitois A, Comte A, Delteil C, Barboule N, Legrand P, Baconnais S, Yin Y, Tadi S, Barbet- Massin E, Berger I, Le Cam E, Modesti M, Rothenberg E, Calsou P, Charbonnier JB. XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non- homologous end joining. Nat Struct Mol Biol (2018) 25(10):971-980
• Frit P, Ropars V, Modesti M, Charbonnier JB, Calsou P. Plugged into the Ku- DNA hub: The NHEJ network. Prog Biophys Mol Biol (2019) 147:62-76
• Chaplin AK, Hardwick SW, Stavridi AK, Buehl CJ, Goff NJ, Ropars V, Liang S, De Oliveira TM, Chirgadze DY, Meek K, Charbonnier JB, Blundell TL. Cryo-EM of NHEJ supercomplexes provides insights into DNA repair. Mol Cell (2021) 81(16):3400-3409.e3