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Biomedical subjects

Michael A McMurray

Publications and source records attributed to Michael A McMurray.

2 recordsLinked to original sources

Aging and genetic instability in yeast.

There is a striking link between increasing age and the incidence of cancer in humans. One of the hallmarks of cancer, genomic instability, has been observed in all types of organisms. In the yeast Saccharomyces cerevisiae, it was recently discovered that during the replicative lifespan, aging cells switch to a state of high genomic instability that persists until they die. In considering these and other recent results, we suggest that accumulation of oxidatively damaged protein in aging cells results in the loss of function of gene products critical for maintaining genome integrity. Determining the identity of these proteins and how they become damaged represents a new challenge for understanding the relationship between age and genetic instability.

Gene Expression Regulation, Fungal↗

An age-induced switch to a hyper-recombinational state.

There is a strong correlation between age and cancer, but the mechanism by which this phenomenon occurs is unclear. We chose Saccharomyces cerevisiae to examine one of the hallmarks of cancer--genomic instability--as a function of cellular age. As diploid yeast mother cells aged, an approximately 100-fold increase in loss of heterozygosity (LOH) occurred. Extending life-span altered neither the onset nor the frequency of age-induced LOH; the switch to hyper-LOH appears to be on its own clock. In young cells, LOH occurs by reciprocal recombination, whereas LOH in old cells was nonreciprocal, occurring predominantly in the old mother's progeny. Thus, nuclear genomes may be inherently unstable with age.

Aging↗