Sidarava, V.; Mearns, S.; Lydall, D.

The ends of linear eukaryotic chromosomes are protected from being recognized as DNA double-strand breaks by telomeres, containing repetitive DNA sequences which bind specific proteins. In humans, mutations in telomere regulatory genes lead to short or long telomere syndromes. These syndromes often show genetic anticipation, where disease has earlier onset and a more severe manifestation in each new generation. Later generations inherit not only the mutation affecting telomere length, but also abnormal length telomeres. Many aspects of telomere length homeostasis are conserved between mammals and yeast. Here we explored telomere length inheritance patterns through the sexual cycle in yeast. Analysis of single telomeres, rather than bulk telomeres, shows that if haploid yeast with short telomeres mate with wild-type yeast creating diploids, short telomere lengths rapidly normalize (within 30 cell divisions). However, long telomeres inherited from one parent can persist for more than 200 mitotic cell divisions. Long telomere can also be transmitted through more than one round of meiosis, independently of mutations that cause long telomeres. These patterns, along with haploinsufficiency effects, show that even in yeast there is a complex relationship between telomere length, telomere length inheritance, and mutations that affect telomere length. Our findings may have implications for families affected by telomere syndromes.