Targeted assembly of ectopic kinetochores to induce chromosome-specific segmental aneuploidies.

ABSTRACT: Cancer cells display persistent underlying chromosomal instability, with individual tumour types intriguingly exhibiting characteristic subsets of whole, and subchromosomal aneuploidies. Few methods to induce specific aneuploidies will exist, hampering investigation of functional consequences of recurrent aneuploidies, as well as the acute consequences of specific chromosome mis-segregation. We therefore investigated the possibility of sabotaging the mitotic segregation of specific chromosomes using nuclease-dead CRISPR-Cas9 (dCas9) as a cargo carrier to specific genomic loci. We recruited the kinetochore-nucleating domain of centromere protein CENP-T to assemble ectopic kinetochores either near the centromere of chromosome 9, or the telomere of chromosome 1. Ectopic kinetochore assembly l

SUBMITTER: Tovini L 

PROVIDER: S-EPMC10183824 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature