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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.
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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...

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Remarkable interference with telomeric function by a G-quadruplex selective bisantrene regioisomer.

Marco Folini1, Claudia Pivetta, Giuseppe Zagotto

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Biochemical Pharmacology
|March 9, 2010
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Summary

Novel anthracene derivatives stabilize G-quadruplex structures, inhibiting telomerase and causing cancer cell dysfunction. The 1,5 and 1,7 substituted analogues show the most promise for targeted cancer therapy.

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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers

Published on: September 19, 2017

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Small molecules stabilizing G-quadruplexes offer selective cancer therapy by inhibiting telomerase.
  • Effective stabilizers require planar aromatic portions for G-quartet stacking and charged side chains for groove interaction.

Purpose of the Study:

  • To evaluate anthracene derivatives with varying side chain positions for G-quadruplex stabilization and telomerase inhibition.
  • To correlate G-quadruplex binding affinity with telomerase inhibition and anti-cancer effects.

Main Methods:

  • Synthesis and evaluation of anthracene derivatives with 4,5-dihydro-1H-imidazol-2-yl-hydrazonic groups at different positions.
  • Assessment of binding affinities to telomeric G-quadruplex.
  • Measurement of telomerase inhibition and cancer cell proliferation/senescence.

Main Results:

  • Regioisomers exhibited distinct G-quadruplex binding affinities; 1,5 and 1,7 bis-substituted analogues were most effective.
  • G-quadruplex binding correlated with telomerase inhibition, indicating interference with telomere processing.
  • The 1,5 isomer inhibited telomerase at lower concentrations than required for cell proliferation reduction.

Conclusions:

  • Anthracene derivatives, particularly 1,5 and 1,7 regioisomers, effectively stabilize G-quadruplexes and inhibit telomerase.
  • Anthracene-induced telomere dysfunction activates senescence pathways, impairing cancer cell growth.
  • These compounds represent promising agents for targeted telomere-based cancer therapy.