PT Unknown AU Pentakota Mr., S TI Insight into the role of CENP-N in kinetcohore structure and function PD 02 PY 2019 DI 10.17185/duepublico/70006 LA en DE Kinetochore AB Accurate chromosome segregation requires the assembly of kinetochores, large multiprotein complexes that are built on the centromeres. A key step in this process involves the assembly of the constitutive centromere-associated network (CCAN) on CENP-A, a histone H3 variant that is enriched at the centromeres. The CCAN is composed of 16 protein components which can be subdivided into four functional groups: the CENP-LN complex, the CENP-HIKM complex, the CENP-OPQUR complex and the CENP-TWSX complex. Two kinetochore proteins, CENP-C and CENP-N are known to specifically recognize CENP-ANCP. Although the CENP-LN complex is known to interact with CENP-ANCP, the mechanistic basis for its interaction with CENP-ANCP or other kinetochore proteins remains poorly understood. This study provides insights into the organization of CENP-LN complex within the CCAN using biochemical, structural and in vivo approaches. Our results unravel the structural basis for the specific recognition of the CENP-A specific L1 loop by CENPN. Additionally, we also have identified that the so-called PEST domain in the Nterminal half of CENP-C (a major component of the CCAN and a direct CENP-A binder), interacts directly with the CENP-LN complex. Furthermore, this study demonstrates that stable and sustained kinetochore localization of the CENP-LN complex requires its interactions with both CENP-ANCP and CENP-C. In summary, this work describes the mechanism by which the CENP-LN complex interacts with CENP-ANCP and CENP-C. The obtained results significantly advance our understanding of the functional role of the CENP-LN complex within the CCAN network, which is required for the kinetochore assembly. ER