Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features.
作者： Susanne MA Lens , Geert JPL Kops , Sarah E McClelland , Karen H Miga , Daniele Fachinetti
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摘要: Intrinsic genomic features of individual chromosomes can contribute to chromosome-specific aneuploidy. Centromeres are key elements for the maintenance chromosome segregation fidelity via a specialized chromatin marked by CENP-A wrapped repetitive DNA. These long stretches DNA vary in length among human chromosomes. Using genetic inactivation cells, we directly interrogate if differences centromere reflect heterogeneity centromeric DNA-dependent and whether this, turn, affects genesis three distinct approaches, show that mis-segregation rates different under conditions compromise function. Whole-genome sequencing mapping combined with cytogenetic analysis, small molecule inhibitors, manipulation revealed inter-chromosomal features, but not length, influences fidelity. We conclude faithful most is biased favor centromeres high abundance components. translate into non-random aneuploidy, hallmark cancer diseases.
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