Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms

Abstract

The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 strains have very short telomeres and very high rates of chromosomal aberrations. Here, we examine genetic stability in tel1 mec1 diploid cells. In the absence of induced DNA damage, these yeast strains had very high frequencies of aneuploidy (both trisomy and monosomy) in addition to elevated rates of chromosome rearrangements. Although we found the aneuploidy in the tel1 mec1 diploids mimicked that observed in bub1 diploids, the tel1 mec1 diploids had a functional spindle assembly checkpoint. Restoration of wild-type telomere lengths in the tel1 mec1 strain substantially reduced the rate of chromosome rearrangements but had no effect on the frequency of aneuploidy.