Related Experiment Video

Updated: Dec 26, 2025

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

10.1K

Methylation of the Suppressor Gene p16INK4a: Mechanism and Consequences

Alfonso Tramontano1, Francesca Ludovica Boffo2, Giusi Russo2

  • 1Department of Precision Medicine University of Campania "L. Vanvitelli", 80131 Naples, Italy.

Biomolecules
|March 19, 2020
PubMed

Insights

DNA damage from transcription-replication conflicts causes promoter methylation of tumor suppressor genes like p16INK4a. This epigenetic silencing removes a key barrier to cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Epigenetics

Background:

  • Tumor suppressor genes in the CDKN2A/B locus (p15INK4b, p16INK4a, p14ARF) are critical barriers against cancer.
  • These genes are frequently silenced or deleted in human cancers, often via DNA methylation of promoter regions.

Purpose of the Study:

  • To investigate the mechanism underlying DNA methylation-induced silencing of the p16INK4a tumor suppressor gene.
  • To explore the link between DNA damage and promoter methylation in cancer development.

Main Methods:

  • Analysis of p16INK4a promoter methylation in relation to DNA damage.
  • Experimental inhibition of replication and transcription processes.
  • Assessment of CpG methylation levels following these interventions.

Main Results:

  • p16INK4a promoter methylation is associated with DNA damage arising from transcription-replication conflicts.
  • Inhibiting replication or transcription significantly reduces both DNA damage and CpG methylation at the p16INK4a promoter.
  • De novo methylation of promoter regions is dependent on local DNA damage.

Conclusions:

  • Local DNA damage, particularly from transcription-replication interference, drives de novo methylation of tumor suppressor gene promoters.
  • This epigenetic silencing of p16INK4a reduces its expression, thereby removing a critical barrier to oncogene-induced senescence and promoting cancer.
  • Understanding this mechanism offers potential targets for cancer prevention and therapy.
Keywords:
DNA damage and repairDNA methylationgene expression

More Related Videos

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.9K
Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

8.7K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.7K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.6K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.3K
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
36.6K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K