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.
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