CENP-B dynamics at centromeres is regulated by a SUMOylation/ubiquitination and proteasomal-dependent degradation mechanism involving the SUMO-targeted ubiquitin E3 ligase RNF4

Centromeric protein B (CENP-B) is a major constituent of the centromere. It is a DNA binding protein that recognizes a specific 17-nt sequence present in the centromeric alphoid satellite repeats. CENP-B importance for centromere stability has only been revealed recently. In addition to its DNA binding properties, CENP-B interacts with the histone H3 variant CENP-A and CENP-C. These interactions confer a mechanical strength to the kinetochore that enables accurate sister chromatids segregation to avoid aneuploidy. Therefore, understanding the mechanisms that regulate CENP-B stability at the centromere is a major unresolved issue for the comprehension of centromere function. In this study, we demonstrate that lysine K402 of CENP-B is a substrate for SUMO post-translational modifications. We show that K402 regulates CENP-B stability at centromeres through a SUMOylation/ubiquitination and proteasomal-dependent degradation mechanism involving the SUMO-Targeted Ubiquitin E3 Ligase RNF4/SNURF. Our study describes SUMOylation of CENP-B as a major post-translational modification involved in centromere dynamics.