bioRxiv · 10.1101/2021.12.16.472883
Specific vulnerability of long telomeres to undergo end fusions revealed by mutational analysis of Rap1
Abstract
The conserved Rap1 protein is part of the shelterin complex that plays critical roles in chromosome end protection and telomere length homeostasis. Previous studies addressed how fission yeast Rap1 contributes to telomere length maintenance, but the mechanism by which the protein inhibits end fusions has remained elusive. Here, we use a genetic screen in combination with high throughput sequencing to identify several amino acid positions in Rap1 that have a key role in end protection. Interestingly, mutations at these sites render cells susceptible to genome instability in a conditional manner with longer telomeres being prone to undergoing end fusions, while short telomeres are sufficiently protected. The protection of long telomeres requires their nuclear envelope attachment mediated by the Rap1-Bqt4 interaction. Our data demonstrates that longer telomeres pose an additional challenge for the maintenance of genome integrity and provides an explanation for a species-specific upper limit in telomere length.
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Baumann, P., Pan, L., Tormey, D., Bobon, N.. 2021-12-16. Specific vulnerability of long telomeres to undergo end fusions revealed by mutational analysis of Rap1. https://doi.org/10.1101/2021.12.16.472883
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