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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.
Replication in Eukaryotes01:29

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 Eukaryotes02:31

Replication in Eukaryotes

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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...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...

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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
12:08

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

Published on: May 22, 2013

Telomere length regulates ISG15 expression in human cells.

Zhenjun Lou1, Jun Wei, Harold Riethman

  • 1Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Aging
|February 17, 2010
PubMed
Summary

Telomere length regulates interferon stimulated gene 15 (ISG15) expression in human cells. Short telomeres increase ISG15, potentially contributing to aging-related inflammation.

Keywords:
ISG15agingcancercell turnoverinflammationtelomere position effect

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Area of Science:

  • Cellular and Molecular Biology
  • Genetics and Genomics
  • Immunology

Background:

  • Telomere length is a critical determinant of cellular lifespan and function.
  • Identifying endogenous genes regulated by telomere length in human cells remains an unmet challenge.
  • Telomere shortening is implicated in aging and age-related diseases.

Purpose of the Study:

  • To identify endogenous genes regulated by telomere length in human cells.
  • To investigate the relationship between telomere length and the expression of interferon stimulated gene 15 (ISG15).
  • To explore the implications of ISG15 regulation by telomere length in the context of human aging.

Main Methods:

  • Analysis of ISG15 expression (RNA and protein) in human cells with varying telomere lengths.
  • Experimental manipulation of telomere length using human telomerase reverse transcriptase (hTERT).
  • Investigation of signaling pathways, including replicative senescence, DNA damage, and type I interferons.
  • Examination of ISG15 expression in human skin specimens from individuals of different ages.

Main Results:

  • Telomere length was found to regulate the expression of interferon stimulated gene 15 (ISG15).
  • ISG15 expression increased in human cells with short telomeres and decreased upon telomere elongation via hTERT.
  • The up-regulation of ISG15 in short-telomere cells was independent of replicative senescence, DNA damage, or type I interferons.
  • ISG15 was observed to be up-regulated in a subset of cells in older individuals' skin specimens.

Conclusions:

  • Endogenous human genes, such as ISG15, can be regulated by telomere length independently of DNA damage signals.
  • Telomere shortening may serve as a mechanism for adjusting cellular physiology.
  • The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states observed in human aging.