Genetic regulation of telomerase in a multiple pathways model to cellular senescence

M Oshimura1, M Shimizu, H Kugoh

  • 1Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University.

Human Cell
|December 1, 1996
PubMed

Insights

Immortal cells trigger senescence in normal cells, suggesting lost genes. Telomerase regulation is one of multiple pathways identified in cellular senescence research.

Area of Science:

  • Cell Biology
  • Genetics

Background:

  • Cellular senescence is a process where normal cells lose their ability to divide.
  • Immortal cells, unlike normal cells, evade senescence due to genetic alterations.
  • Senescence involves complex genetic pathways and gene regulation.

Purpose of the Study:

  • To investigate the role of specific genes in the senescence program.
  • To determine if telomerase regulation is a key pathway in cellular senescence.
  • To analyze the relationship between senescence, telomerase activity, and telomere length.

Main Methods:

  • Microcell fusion was used to introduce normal human chromosomes into immortal cells.
  • Telomerase activity was measured in microcell hybrids.
  • Terminal Restriction Fragment (TRF) length was analyzed to assess telomere length.

Main Results:

  • Hybrids between immortal and normal cells exhibited senescence.
  • Introduction of chromosomes led to senescence, with or without loss of telomerase activity.
  • Telomere shortening was observed in some hybrids, correlating with senescence.

Conclusions:

  • Multiple genetic loci and pathways are involved in cellular senescence.
  • Telomerase regulation represents one of several mechanisms controlling cellular senescence.
  • Gene inactivation or mutation in immortal cells disrupts the senescence program.

Related Concept Videos

Replication in Eukaryotes02:31

Replication in Eukaryotes

Overview
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...
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...
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...