Nov 9, 2018

Dynamics of age-related catastrophic mitotic failures and recovery in yeast

BioRxiv : the Preprint Server for Biology
Matthew M CraneMatt Kaeberlein

Abstract

Genome instability is a hallmark of aging and contributes to age-related disorders such as progeria, cancer, and Alzheimer's disease. Cell cycle checkpoints have generally been studied in young cells and animals where genomic instability is low. Here, we use single-cell imaging to study consequences of increased genomic instability during aging, and identify striking age-associated genome missegregation events where the majority of chromatin is mistakenly sent to the daughter cell. A transient cell cycle arrest that can persist for many hours, as cells engage a retrograde transport mechanism to return chromosomes to the mother cell, accompanies this breakdown in mitotic fidelity. The repetitive ribosomal DNA (rDNA) has been previously identified as being highly vulnerable to age-related replication stress, and we present several lines of evidence supporting a model whereby expansion of rDNA during aging results in nucleolar breakdown and competition for limited nucleosomes, thereby increasing risk of catastrophic genome missegregation.

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Mentioned in this Paper

Nucleosomes
Pain Catastrophizing
Genome
Virus Replication
DNA, Ribosomal
Yeasts
Alzheimer's Disease
Nucleosome Location
Cell Growth
Nucleolar

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