Rap1 protein regulates telomere turnover in yeast

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Telomere length is crucial for genomic stability, maintained by a balance of DNA addition and loss.
• Telomere regulation involves telomerase and a protein-DNA complex, with Rap1p previously implicated in negative telomere length control in yeast.
• The C-terminal tail of Rap1p is hypothesized to limit telomerase access to chromosome ends.

Purpose of the Study:

• To investigate the role of the Rap1p C-terminal tail in regulating telomere length dynamics in Kluyveromyces lactis.
• To elucidate the mechanism by which Rap1p controls telomeric repeat turnover at chromosome ends.

Main Methods:

• Generated Kluyveromyces lactis mutants with truncations in the Rap1p C-terminal tail (Rap1p-DeltaC).
• Introduced a telomerase template mutation (ter1-kpn) to alter telomeric repeat addition.
• Analyzed telomere length regulation and repeat turnover in single and double mutant strains.

Main Results:

• Truncating the Rap1p C-terminal tail accelerated telomeric repeat turnover in the distal telomere region.
• Combining the Rap1p-DeltaC mutation with the ter1-kpn mutation led to a synergistic loss of telomere length regulation.
• Restoring functional telomeric repeats to unregulated telomeres re-established telomere length control.

Conclusions:

• The C-terminal tail of Rap1p plays a critical role in regulating telomere length.
• Rap1p controls the rate of terminal telomere turnover through interactions with distal telomeric repeats.
• This interaction is essential for limiting telomerase access and maintaining telomere length homeostasis.