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Telomeres and Telomerase

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 Telomerase

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.

Replication in Eukaryotes

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
Eukaryotic replication follows many of the same...

Replication in Eukaryotes

Replication in Eukaryotes

Replicative Cell Senescence

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...

Restarting Stalled Replication Forks

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...

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Related Experiment Video

Updated: Jul 6, 2026

Analyzing Telomeric Protein-DNA Interactions Using Single-Molecule Magnetic Tweezers

Analyzing Telomeric Protein-DNA Interactions Using Single-Molecule Magnetic Tweezers

Published on: August 30, 2024

Flap endonuclease 1 contributes to telomere stability.

Abhishek Saharia¹, Lionel Guittat, Sandra Crocker

¹Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.

Current Biology : CB

|April 9, 2008

Summary

Flap endonuclease 1 (FEN1) depletion causes telomere instability and loss. Restoring telomerase activity or FEN1

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Published on: April 13, 2015

Area of Science:

Genetics
Molecular Biology
Cell Biology

Background:

Telomere stability is crucial for genomic integrity.
Flap endonuclease 1 (FEN1) is involved in DNA replication and repair.
FEN1's role in telomere maintenance is not fully understood.

Purpose of the Study:

To investigate the role of FEN1 in telomere stability.
To determine the mechanisms by which FEN1 affects telomeres.

Main Methods:

FEN1 depletion in cells.
Analysis of telomere dysfunction markers (e.g., gammaH2AX, sister telomere loss).
Telomerase activity rescue experiments.
Genetic rescue using FEN1 mutants.

Main Results:

FEN1 depletion leads to telomere dysfunction, including gammaH2AX foci and sister telomere loss.
Active telomerase expression rescues FEN1 depletion-induced telomere dysfunction.
FEN1 depletion specifically affects telomeres replicated by lagging-strand DNA replication.
FEN1's nuclease activity and interaction with WRN and TRF2 are essential for its telomeric function.

Conclusions:

FEN1 is critical for maintaining telomere stability.
FEN1 ensures efficient lagging-strand telomere replication.
FEN1's nuclease activity and protein interactions are key to its telomere maintenance role.