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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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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...
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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...
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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.
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Droplet Digital TRAP ddTRAP: Adaptation of the Telomere Repeat Amplification Protocol to Droplet Digital Polymerase Chain Reaction
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Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene.

Tao Xu1,2, De Cheng1, Yuanjun Zhao3

  • 1College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA 99210.

Proceedings of the National Academy of Sciences of the United States of America
|June 22, 2021
PubMed
Summary
This summary is machine-generated.

A novel enhancer element, VNTR2-1, regulates human telomerase reverse transcriptase (hTERT) expression, impacting telomere length and aging. Its variations influence human aging and susceptibility to age-related diseases.

Keywords:
hTERT genehuman longevitypolymorphism and genetic diversitiesrepetitive DNA elementstelomere and telomerase

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Area of Science:

  • Genetics
  • Molecular Biology
  • Aging Research

Background:

  • Genome-wide association studies link hTERT locus variants to telomere length and cancer risk.
  • The regulation of hTERT expression is crucial for maintaining telomere homeostasis and cellular function.

Purpose of the Study:

  • To identify and characterize novel regulatory elements within the hTERT locus.
  • To investigate the role of VNTR2-1 in hTERT transcription and its functional consequences.

Main Methods:

  • Identification of an intronic variable number tandem repeat (VNTR2-1) with enhancer-like properties.
  • Assays to determine VNTR2-1's effect on hTERT transcription in a chromatin-dependent manner.
  • Genomic deletion of VNTR2-1 in melanoma cells and analysis of resulting phenotypes.

Main Results:

  • VNTR2-1 acts as an enhancer, activating hTERT transcription via cooperation with the proximal promoter and basic helix-loop-helix transcription factors.
  • Deletion of VNTR2-1 reduces hTERT transcription, leading to telomere shortening, senescence, and impaired tumor growth.
  • VNTR2-1 length variation in human populations correlates with aging, with shorter alleles underrepresented in centenarians.

Conclusions:

  • VNTR2-1 is a key polymorphic regulatory element in the telomerase network, influencing telomere homeostasis and age-related disease susceptibility.
  • This finding provides a molecular basis for genetic diversity in aging and disease risk.