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XB-ART-59799
J Cell Biol 2023 Jun 05;2226:. doi: 10.1083/jcb.202110124.
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Repression of CENP-A assembly in metaphase requires HJURP phosphorylation and inhibition by M18BP1.

Flores Servin JC , Brown RR , Straight AF .


Abstract
Centromeres are the foundation for mitotic kinetochore assembly and thus are essential for chromosome segregation. Centromeres are epigenetically defined by nucleosomes containing the histone H3 variant CENP-A. CENP-A nucleosome assembly is uncoupled from replication and occurs in G1, but how cells control this timing is incompletely understood. The formation of CENP-A nucleosomes in vertebrates requires CENP-C and the Mis18 complex which recruit the CENP-A chaperone HJURP to centromeres. Using a cell-free system for centromere assembly in X. laevis egg extracts, we discover two activities that inhibit CENP-A assembly in metaphase. HJURP phosphorylation prevents the interaction between HJURP and CENP-C in metaphase, blocking the delivery of soluble CENP-A to centromeres. Non-phosphorylatable mutants of HJURP constitutively bind CENP-C in metaphase but are not sufficient for new CENP-A assembly. We find that the M18BP1.S subunit of the Mis18 complex also binds to CENP-C to competitively inhibit HJURP's access to centromeres. Removal of these two inhibitory activities causes CENP-A assembly in metaphase.

PubMed ID: 37141119
PMC ID: PMC10165474
Article link: J Cell Biol
Grant support: [+]

Genes referenced: mbp mis18bp1 myc
GO keywords: chromosome segregation [+]


Article Images: [+] show captions
References [+] :
Barnhart, HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. 2011, Pubmed