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bioRxiv · 10.1101/757864

Loss of Cdc13 causes genome instability by deficiency in replication-dependent telomere capping

Langston, R.·Palazzola, D.·Bonnell, E.·Wellinger, R. J.·Weinert, T.
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Abstract

In budding yeast, Cdc13, Stn1, and Ten1 form a telomere binding heterotrimer dubbed CST. Here we investigate the role of Cdc13/CST in maintaining genome stability, using a Chr VII disome system that can generate recombinants, loss, and enigmatic unstable chromosomes. In cells expressing a temperature sensitive CDC13 allele, cdc13F684S, unstable chromosomes frequently arise due to problems in or near a telomere. Hence, when Cdc13 is defective, passage through S phase causes Exo1-dependent ssDNA and unstable chromosomes, which then are the source for whole chromosome instability events (e.g. recombinants, chromosome truncations, dicentrics, and/or loss). Specifically, genome instability arises from a defect in Cdc13s replication-dependent telomere capping function, not Cdc13s putative post-replication telomere capping function. Furthermore, the unstable chromosomes form without involvement of homologous recombination nor non-homologous end joining. Our data suggest that a Cdc13/CST defect in semi-conservative replication near the telomere leads to ssDNA and unstable chromosomes, which then are lost or subject to complex rearrangements. This system defines a links between replication-dependent chromosome capping and genome stability in the form of unstable chromosomes.

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Langston, R., Palazzola, D., Bonnell, E., Wellinger, R. J., Weinert, T.. 2019-09-05. Loss of Cdc13 causes genome instability by deficiency in replication-dependent telomere capping. https://doi.org/10.1101/757864

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