DNA damage checkpoint activation impairs chromatin homeostasis and promotes mitotic catastrophe during aging.

ABSTRACT: Genome instability is a hallmark of aging and contributes to age-related disorders such as cancer and Alzheimer's disease. The accumulation of DNA damage during aging has been linked to altered cell cycle dynamics and the failure of cell cycle checkpoints. Here, we use single cell imaging to study the consequences of increased genomic instability during aging in budding yeast and identify striking age-associated genome missegregation events. This breakdown in mitotic fidelity results from the age-related activation of the DNA damage checkpoint and the resulting degradation of histone proteins. Disrupting the ability of cells to degrade histones in response to DNA damage increases replicative lifespan and reduces genomic missegregations. We present several lines of evidence supporting a mod

SUBMITTER: Crane MM 

PROVIDER: S-EPMC6850777 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature