Andrea Scelfo, Annapaola Angrisani, Marco Grillo, Bethany M Barnes, Francesc Muyas, Carolin M Sauer, Chin Wei Brian Leung, Marie Dumont, Marine Grison, David Mazaud, Mickaël Garnier, Laetitia Guintini, Louisa Nelson, Fumiko Esashi, Isidro Cortés-Ciriano, Stephen S Taylor, Jérôme Déjardin, Therese Wilhelm, Daniele Fachinetti
The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities. Mechanistically, we unveil unique dynamics of the centromeric replisome distinct from the rest of the genome...
February 7, 2024: Molecular Cell