Structural and functional insights into yeast Tbf1 as an atypical telomeric repeat-binding factor

Area of Science:

• Molecular biology
• Structural biology
• Genetics

Background:

• Telomeric repeat-binding factor 1 (Tbf1) shares structural similarities with telomeric repeat-binding factors (TRFs) and influences telomere homeostasis and ribosome regulation.
• The molecular mechanisms underlying Tbf1's distinct functions compared to other TRFs are not fully understood.

Purpose of the Study:

• To elucidate the structural basis of Schizosaccharomyces pombe Tbf1 (spTbf1) function.
• To investigate the role of spTbf1 domains in telomeric DNA binding and protein interactions.

Main Methods:

• X-ray crystallography to determine the structures of spTbf1's TRF homology (TRFH) and Myb-L domains.
• Biochemical assays to analyze spTbf1's DNA-binding capabilities and interactions.

Main Results:

• The crystal structures of spTbf1 TRFH and Myb-L domains were determined.
• TRFH-mediated homodimerization is crucial for spTbf1 stability.
• spTbf1's TRFH domain lacks the conserved docking motif for shelterin complex interaction.
• spTbf1 recognizes S. pombe telomeric double-stranded DNA through a coordinated effort of its TRFH, Myb-L domains, and a loop region.

Conclusions:

• spTbf1 functions as an atypical telomeric repeat-binding factor in fungi.
• The structural basis for spTbf1's unique role, distinct from shelterin components, is revealed.
• These findings offer insights into the evolution of TRFH-containing telomeric proteins.