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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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Replication in Eukaryotes

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
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Overview
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

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Analyzing Telomeric Protein-DNA Interactions Using Single-Molecule Magnetic Tweezers
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TEN1 is essential for CDC13-mediated telomere capping.

Ling Xu1, Ruben C Petreaca, Hovik J Gasparyan

  • 1Department of Cell Biology, University of California, Riverside, California 92521, USA.

Genetics
|September 16, 2009
PubMed
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Ten1 protein is crucial for maintaining telomere integrity in yeast by working with Cdc13. Loss of Ten1 function leads to telomere damage, highlighting its essential role in end protection and DNA replication.

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Area of Science:

  • Cell biology
  • Molecular genetics
  • Biochemistry

Background:

  • Telomere binding proteins like Cdc13 are essential for chromosome end protection and length maintenance in Saccharomyces cerevisiae.
  • The roles of Ten1 and Stn1, which interact with Cdc13, in telomere integrity are not fully understood.
  • Ten1's function in preventing aberrant single-stranded telomere DNA accumulation requires clarification regarding end protection versus replication defects.

Purpose of the Study:

  • To investigate the function of Ten1 in telomere maintenance and end protection using temperature-sensitive mutants.
  • To elucidate the relationship between Ten1, Cdc13, and telomere integrity.
  • To determine if Ten1 has roles independent of Cdc13.

Main Methods:

  • Analysis of ten1 temperature-sensitive (ts) mutants in Saccharomyces cerevisiae.
  • Observation of telomere length and single-stranded DNA accumulation under permissive and non-permissive conditions.
  • Investigation of Cdk1 activity, EXO1 nuclease, Rad52-YFP foci, and synthetic interactions with POLalpha complex mutations.

Main Results:

  • ten1-ts mutants exhibit elongated telomeres at permissive temperatures and accumulate extensive single-stranded telomeric DNA at non-permissive temperatures.
  • Cdk1 activity is required for single-stranded DNA formation, and EXO1 deletion partially suppresses growth defects, suggesting end protection defects.
  • Ten1 promotes de novo telomere addition, and its absence leads to DNA repair foci and synthetic lethality with POLalpha mutations, indicating a critical role in end protection and DNA replication.

Conclusions:

  • Ten1 is essential for Cdc13-mediated telomere end protection and promotes de novo telomere addition.
  • Cdc13 binding to telomeres is insufficient for end protection without functional Ten1.
  • Ten1 may also have a Cdc13-independent role in DNA replication.