%0 Journal Article
%T Loss of Cdc13 causes genome instability by a deficiency in replication-dependent telomere capping
%A Dominic Palazzola
%A Erin Bonnell
%A Rachel E. Langston
%A Raymund J. Wellinger
%A Ted Weinert
%J -
%D 2020
%R 10.1371/journal.pgen.1008733
%X In budding yeast, Cdc13, Stn1, and Ten1 form the telomere-binding heterotrimer CST complex. Here we investigate the role of Cdc13/CST in maintaining genome stability by using a Chr VII disome system that can generate recombinants, chromosome loss, and enigmatic unstable chromosomes. In cells expressing a temperature sensitive CDC13 allele, cdc13F684S, unstable chromosomes frequently arise from problems in or near a telomere. We found that, when Cdc13 is defective, passage through S phase causes Exo1-dependent ssDNA and unstable chromosomes that are then the source for additional chromosome instability events (e.g. recombinants, chromosome truncations, dicentrics, and/or chromosome loss). We observed that genome instability arises from a defect in Cdc13¡¯s function during DNA replication, not Cdc13¡¯s putative post-replication telomere capping function. The molecular nature of the initial unstable chromosomes formed by a Cdc13-defect involves ssDNA and does not involve homologous recombination nor non-homologous end joining; we speculate the original unstable chromosome may be a one-ended double strand break. This system defines a link between Cdc13¡¯s function during DNA replication and genome stability in the form of unstable chromosomes, that then progress to form other chromosome changes
%K Chromosome structure and function
%K Telomeres
%K Genetic networks
%K Cell cycle and cell division
%K Protein structure networks
%K Synthesis phase
%K DNA replication
%K DNA recombination
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008733