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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.

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...

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

Condensins

Condensins

Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...

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Related Experiment Video

Updated: Jul 5, 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

Telomere dysfunction and cell survival: roles for distinct TIN2-containing complexes.

Sahn-Ho Kim¹, Albert R Davalos, Seok-Jin Heo

¹Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. skim3@hfhs.org

The Journal of Cell Biology

|April 30, 2008

Summary

Distinct TIN2 protein complexes maintain telomeres. The TIN2-15C mutant protein causes telomere uncapping and cell death, especially when p53 is absent, highlighting TIN2

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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

Area of Science:

Cell Biology
Molecular Biology
Genetics

Background:

Telomeres, the protective caps of chromosomes, are maintained by a complex of proteins including TRF1, TRF2, and POT1.
TRF1-interacting protein 2 (TIN2) is a key component, interacting with TRF1, TRF2, and POT1, potentially forming a core telomere maintenance complex with TPP1 and hRap1.

Purpose of the Study:

To investigate the existence and function of distinct TIN2 protein subcomplexes in human cells.
To determine the in vivo roles of specific TIN2 subcomplexes in telomere maintenance and cellular responses to DNA damage.

Main Methods:

Isolation of TIN2 subcomplexes from nuclear lysates of both unperturbed human cells and cells expressing specific TIN2 mutants (TIN2-13 and TIN2-15C).
Assessment of telomere uncapping, telomere dysfunction, growth arrest, and cell death in response to TIN2 mutations in cells with and without functional p53.

Main Results:

Evidence for two distinct TIN2 subcomplexes with differing functions was found.
TIN2-15C, a mutant unable to bind TRF1, was more potent than TIN2-13 (unable to bind TRF2) in inducing telomere uncapping and growth arrest in p53-proficient cells.
TIN2-15C induced greater telomere dysfunction and cell death than TIN2-13 in p53-deficient cells, suggesting a critical role in cell survival.

Conclusions:

Distinct TIN2-containing complexes exist and play specific roles in telomere maintenance.
TIN2 subcomplexes sensitive to the TIN2-15C mutation are crucial for cell survival, particularly in the absence of functional p53.
These findings elucidate the functional heterogeneity of TIN2 complexes and their interplay with the p53 pathway in maintaining genomic stability.