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Related Experiment Videos

Cdc13 both positively and negatively regulates telomere replication.

A Chandra1, T R Hughes, C I Nugent

  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

Genes & Development
|March 7, 2001
PubMed
Summary

Cdc13 protein regulates yeast telomere replication. It first recruits telomerase and then limits G-strand synthesis, coordinating both DNA strands for proper replication.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Cdc13 is a key protein in yeast telomere replication, known to recruit telomerase to chromosome ends.
  • A specific site on Cdc13 is crucial for this positive regulation, and its mutation (cdc13-2) disrupts telomere replication.
  • Telomeres are protective caps at the ends of chromosomes that shorten with each cell division.

Purpose of the Study:

  • To investigate a newly identified mutation (cdc13-5) in Cdc13 to understand its role in negative regulation of telomere replication.
  • To elucidate the mechanism by which Cdc13 coordinates the synthesis of both DNA strands at telomeres.
  • To determine the interaction between Cdc13, Stn1, and telomerase in regulating telomere length.

Main Methods:

  • Analysis of the cdc13-5 mutant in yeast.

Related Experiment Videos

  • Investigating the interaction between Cdc13 and Stn1.
  • Studying the effect of altered Cdc13 function on telomere elongation and DNA strand synthesis coordination.

    • Main Results:

    • The cdc13-5 mutation reveals a separate negative regulatory role for Cdc13 in telomere replication.
    • Loss of this negative regulation leads to excessive G-strand elongation and impaired C-strand synthesis coordination.
    • Increased Stn1 expression suppresses telomere elongation defects caused by cdc13-5 and DNA polymerase alpha mutations.
    • The cdc13-2 mutation disrupts both Cdc13-telomerase and Cdc13-Stn1 interactions.

    Conclusions:

    • Cdc13 acts as a dual regulator of telomere replication, first promoting and then inhibiting telomere elongation.
    • Cdc13 coordinates lagging strand (C-strand) synthesis with telomere replication through its interaction with Stn1.
    • Overlapping binding sites on Cdc13 for telomerase and Stn1 dictate its sequential positive and negative regulatory roles.