Structure of Centromeric Chromatin and Its Consequences for Genome Stability
Carlos Sacristán López
Hubrecht Institute, Utrech (Netherlands)
The condensation of chromatin by Structural Maintenance of Chromosome (SMC) complexes during mitosis is essential for ensuring accurate chromosome segregation. A key aspect of this process is the 3D organization of the centromere—the chromosomal region responsible for kinetochore assembly and the attachment of sister chromatids to spindle microtubules. Disruption of centromere architecture compromises these attachments, resulting in chromosome segregation errors and aneuploidy—hallmarks of cancer.
In our recent work, we revealed that SMC complexes fold centromeric chromatin into two distinct subdomains during mitosis. This structural arrangement has important implications for kinetochore function, as it divides the kinetochore into two independent microtubule-binding domains. I will present evidence that misregulation of this organization impairs kinetochore function, promoting chromosome missegregation and, under specific conditions, centromeric DNA breakage.