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An Age-Induced Switch to a Hyper-Recombinational State
Michael A. McMurray and
Daniel E. Gottschling*
There is a strong correlation between age and cancer, but themechanism by which this phenomenon occurs is unclear. We choseSaccharomyces cerevisiae to examine one of the hallmarks ofcancer—genomic instability— as a function of cellularage. As diploid yeast mother cells aged, an 100-fold increasein loss of heterozygosity (LOH) occurred. Extending life-spanaltered neither the onset nor the frequency of age-induced LOH;the switch to hyper-LOH appears to be on its own clock. In youngcells, LOH occurs by reciprocal recombination, whereas LOH inold cells was nonreciprocal, occurring predominantly in theold mother's progeny. Thus, nuclear genomes may be inherentlyunstable with age.
Division of Basic Sciences, The Fred Hutchinson Cancer Research Center, and Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98109, USA.
* To whom correspondence should be addressed. E-mail: dgottsch{at}fhcrc.org
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DNA end joining becomes less efficient and more error-prone during cellular senescence.
A. Seluanov, D. Mittelman, O. M. Pereira-Smith, J. H. Wilson, and V. Gorbunova (2004)
PNAS
101, 7624-7629
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The Transcriptome of Prematurely Aging Yeast Cells Is Similar to That of Telomerase-deficient Cells.
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. 
