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The ATAD2/ANCCA homolog Yta7 cooperates with Scm3 <sup>HJURP</sup> to deposit Cse4 <sup>CENP-A</sup> at the centromere in yeast

Sara Shahnejat‐Bushehri, Ann E. Ehrenhofer‐Murray

2020Proceedings of the National Academy of Sciences23 citationsDOIOpen Access PDF

Abstract

Significance Centromeres are the sites on the chromosome where kinetochores are assembled, a process that is required for faithful chromosome segregation. Nucleosomes in centromeric chromatin contain the histone H3 variant CENP-A. Here, we have identified the AAA + ATPase Yta7/ATAD2 as a deposition factor for CENP-A at centromeres in yeast. Our findings indicate that Yta7 acts as a hexameric AAA + ATPase that unfolds CENP-A/H4 and hands it over to Scm3/HJURP for incorporation into the centromeric nucleosome. Defects in this process result in kinetochore instability and chromosome segregation defects. The human homolog ATAD2 is frequently overexpressed in cancer cells, suggesting that it contributes to carcinogenesis by impairing chromosome segregation.

Topics & Concepts

CentromereChromosome segregationKinetochoreNucleosomeChromatinBiologyChromosomeHistoneCell biologyHistone H3Saccharomyces cerevisiaeGeneticsMolecular biologyDNAYeastGeneChromosomal and Genetic VariationsGenomics and Chromatin DynamicsUbiquitin and proteasome pathways