Loss of Cdc13 causes genome instability by a deficiency in replication-dependent telomere capping release_qmmgcsqf55c5phfkrldhjpzmwu

by Rachel E Langston, Dominic Palazzola, Erin Bonnell, Raymund J. Wellinger, Ted Weinert

Published in PLoS Genetics by Public Library of Science (PLoS).

2020   Volume 16, Issue 4, e1008733

Abstract

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.
In text/plain format

Archived Files and Locations

application/pdf  4.2 MB
file_lljmwedqcveytjnh5g5bcx4oty
journals.plos.org (publisher)
web.archive.org (webarchive)
Read Archived PDF
Preserved and Accessible
Type  article-journal
Stage   published
Date   2020-04-14
Language   en ?
Container Metadata
Open Access Publication
In DOAJ
In ISSN ROAD
In Keepers Registry
ISSN-L:  1553-7390
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
Catalog Record
Revision: 6a617c2e-8c9f-43ec-b204-7496f8d12d19
API URL: JSON