Decoding the centromeric nucleosome through CENP-N

eLife

Karolin Luger¹  Keda Zhou²  Garry P Morgan³  Andrea Musacchio⁴  Satyakrishna Pentakota⁴  Ingrid R Vetter⁴  Charlotte Smith⁴  Arsen Petrovic⁴  Stefano Maffini⁴  John R Weir⁴ 

[1] Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany;Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, United States;Department of MCDB, University of Colorado at Boulder, Boulder, United States;Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany;

关键词: centromere;    kinetochore;    CENP-A;    CENP-N;    CENP-C;    mitosis;   

DOI  :  10.7554/eLife.33442

来源: DOAJ

【 摘 要 】

Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.

【 授权许可】

Unknown