Dynamic cell cycle–dependent phosphorylation modulates CENP-L–CENP-N centromere recruitment

Despite being constitutively localized to centromeres, the DNA proximal components of the kinetochore undergo substantial remodeling throughout the cell cycle. We highlight the role of cell cycle-dependent phosphorylation in regulating the interactions and localization of the CENP-LN complex. The ki...

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Bibliographic Details
Published in:	Molecular biology of the cell 2022-09, Vol.33 (10), p.1-ar87
Main Authors:	Navarro, Alexandra P, Cheeseman, Iain M
Format:	Article
Language:	eng
Subjects:	Analysis Cell cycle Centromeres Chromosomes Identification and classification Phosphorylation Properties Proteins
Online Access:	Get full text
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Summary:	Despite being constitutively localized to centromeres, the DNA proximal components of the kinetochore undergo substantial remodeling throughout the cell cycle. We highlight the role of cell cycle-dependent phosphorylation in regulating the interactions and localization of the CENP-LN complex. The kinetochore is a macromolecular structure that is needed to ensure proper chromosome segregation during each cellular division. The kinetochore is assembled upon a platform of the 16-subunit constitutive centromere-associated network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics needed to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN complex is a CCAN component that displays unique cell cycle–dependent localization behavior, peaking in the S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle–dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at kinetochores to enable cell cycle–dependent CCAN reorganization.
ISSN:	1059-1524 1939-4586