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Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
The Cell Cycle Control System01:28

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The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
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The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
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Published on: April 4, 2025

A G-quadruplex stabilizer induces M-phase cell cycle arrest.

Yuan-Chin Tsai1, Haiyan Qi, Chao-Po Lin

  • 1Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.

The Journal of Biological Chemistry
|June 18, 2009
PubMed
Summary

HXDV, a G-quadruplex stabilizer, shows antiproliferative and apoptotic effects independent of telomerase. This compound also acts as an M-phase blocker, halting cell cycle progression through G-quadruplex binding.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Drug Discovery

Background:

  • G-quadruplex (G4) stabilizers like telomestatin have shown antiproliferative and anti-tumor activities.
  • These activities are often attributed to telomerase inhibition or telomere dysfunction.

Purpose of the Study:

  • To investigate the antiproliferative and apoptotic effects of HXDV, a telomestatin analog.
  • To determine the mechanism of action of HXDV, particularly its effect on cell cycle progression and its dependence on G-quadruplex binding.

Main Methods:

  • Cell proliferation assays
  • Apoptosis assays
  • Cell cycle analysis (DNA content, mitotic index)
  • Immunofluorescence microscopy (centrosomes, histone H3 phosphorylation, spindle fibers)
  • Western blotting (Aurora A expression)
  • Time-lapse microscopy
  • Comparison with a non-G-quadruplex binding analog (TXTLeu)

Main Results:

  • HXDV exhibits antiproliferative activity and induces apoptosis in both telomerase-positive and -negative cells.
  • HXDV causes M-phase cell cycle arrest, evidenced by 4n DNA content, increased mitotic index, centrosome separation, and defective chromosome alignment.
  • HXDV reduces Aurora A expression and its effects are dependent on G-quadruplex binding activity.

Conclusions:

  • HXDV possesses potent antiproliferative and apoptotic activities.
  • HXDV is a novel M-phase blocker, independent of telomerase inhibition.
  • The G-quadruplex binding capability of HXDV is crucial for its observed cellular effects.