Cdc13 N-terminal dimerization, DNA binding, and telomere length regulation.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Cdc13 is essential for yeast chromosome end replication and genome integrity.
• Its N-terminal domain (Cdc13N) role in telomere length regulation is not fully understood.

Purpose of the Study:

• To structurally, biochemically, and functionally characterize the Cdc13 N-terminal domain (Cdc13N).
• To elucidate the role of Cdc13N in telomere length regulation.

Main Methods:

• X-ray crystallography for structural analysis.
• Biochemical assays for DNA binding and dimerization studies.
• In vivo functional analysis using point mutations in full-length Cdc13.

Main Results:

• Cdc13N possesses an oligonucleotide/oligosaccharide binding (OB) fold and mediates Cdc13 dimerization.
• Cdc13N weakly binds long, single-stranded telomeric DNA, dependent on domain oligomerization.
• Mutations disrupting Cdc13N dimerization or DNA binding altered telomere length in vivo.

Conclusions:

• Cdc13N dimerization and DNA binding are critical for proper telomere length regulation.
• The dimeric nature and multiple DNA-binding domains of Cdc13 are key for coordinating telomerase recruitment and activity at telomeres.