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CDK phosphorylation of Xenopus laevis M18 BP 1 promotes its metaphase centromere localization
Author(s) -
French Bradley T,
Straight Aaron F
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100093
Subject(s) - kinetochore , metaphase , centromere , biology , mitosis , xenopus , library science , microbiology and biotechnology , genetics , chromosome , computer science , gene
Chromosome segregation requires the centromere, the site on chromosomes where kinetochores assemble in mitosis to attach chromosomes to the mitotic spindle. Centromere identity is defined epigenetically by the presence of nucleosomes containing the histone H3 variant CENP ‐A. New CENP ‐A nucleosome assembly occurs at the centromere every cell cycle during G1, but how CENP ‐A nucleosome assembly is spatially and temporally restricted remains poorly understood. Centromere recruitment of factors required for CENP ‐A assembly is mediated in part by the three‐protein Mis18 complex (Mis18α, Mis18β, M18 BP 1). Here, we show that Xenopus M18 BP 1 localizes to centromeres during metaphase—prior to CENP ‐A assembly—by binding to CENP ‐C using a highly conserved SANTA domain. We find that Cdk phosphorylation of M18 BP 1 is necessary for M18 BP 1 to bind CENP ‐C and localize to centromeres in metaphase. Surprisingly, mutations which disrupt the metaphase M18 BP 1/ CENP ‐C interaction cause defective nuclear localization of M18 BP 1 in interphase, resulting in defective CENP ‐A nucleosome assembly. We propose that M18 BP 1 may identify centromeric sites in metaphase for subsequent CENP ‐A nucleosome assembly in interphase.