Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

4.6K
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...
4.6K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.3K
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...
9.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

35.6K
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.
35.6K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

5.9K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Epigenetic Regulation01:37

Epigenetic Regulation

3.1K
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...
3.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

<i>Ex vivo</i> localization of wireless implantable microdevice using high-resolution 3D imaging techniques.

Frontiers in bioengineering and biotechnology·2026
Same author

Molecular Evaluation of RNA-Based Immune Checkpoint Profiling in Clear Cell Renal Cell Carcinoma.

Journal of clinical medicine·2026
Same author

Extracellular serine availability regulates inflammatory skin phenotypes.

Biology direct·2026
Same author

HnRNP C binding to inverted <i>Alu</i> elements protects the transcriptome from pre-mRNA circularization.

Science advances·2026
Same author

Beyond Histology: Tensiomyography as an Integrated Measure of Muscle Function in Osteoporotic and Osteoarthritic Patients.

Journal of clinical medicine·2026
Same author

Medulloblastoma response to mevalonate pathway inhibition is independent of p53 status.

Biology direct·2026
Same journal

Defining and characterizing the relevant state variables of the mammalian gut ecosystem.

Cell reports·2026
Same journal

Distinct compositional changes but shared quantitative microbiome and anti-inflammatory modulations by diet.

Cell reports·2026
Same journal

HPD is a copper-binding protein that interacts with DLAT to promote colorectal cancer cuproptosis under copper stress.

Cell reports·2026
Same journal

Rotational trophoblast organoids reveal biomechanical regulation of trophoblast differentiation.

Cell reports·2026
Same journal

Dysregulated calcium signaling underlies hyposalivation and microbial dysbiosis in Down syndrome.

Cell reports·2026
Same journal

Collagen 1-mediated CXCL1 secretion in tumor cells activates fibroblasts to promote radioresistance of esophageal cancer.

Cell reports·2026
See all related articles

Related Experiment Video

Updated: Aug 23, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.6K

Metabolic regulation by p53 prevents R-loop-associated genomic instability.

Emanuele Panatta1, Alessio Butera2, Eleonora Mammarella1

  • 1Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133 Rome, Italy.

Cell Reports
|November 2, 2022
PubMed
Summary
This summary is machine-generated.

The tumor suppressor p53 maintains genomic stability by regulating S-adenosylmethionine (SAM) levels. p53 deficiency impairs DNA methylation and causes genomic instability, which SAM repletion can reverse.

Keywords:
CP: Molecular biologycancerchromosome stabilityepigenetic integrityp53tumor suppression

More Related Videos

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts
10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

7.3K
Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication
05:55

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication

Published on: August 23, 2024

612

Related Experiment Videos

Last Updated: Aug 23, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.6K
Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts
10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

7.3K
Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication
05:55

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication

Published on: August 23, 2024

612

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Gene-environment interactions can alter the epigenome, contributing to cancer development.
  • The tumor suppressor p53 plays a critical role in maintaining genomic integrity.
  • Epigenetic dysregulation, including DNA methylation, is implicated in cancer pathogenesis.

Purpose of the Study:

  • To investigate the role of the tumor suppressor p53 in maintaining genomic integrity through epigenetic regulation.
  • To elucidate the connection between p53, S-adenosylmethionine (SAM) levels, and cancer-related genomic instability.
  • To understand the molecular mechanisms by which p53 influences one-carbon metabolism and SAM synthesis.

Main Methods:

  • Integration of epigenomics, transcriptomics, and metabolic analyses.
  • Functional perturbation studies in p53-deficient cells.
  • Analysis of DNA methylation, heterochromatin, histone modifications (H3K9 methylation), and satellite RNA expression.
  • Assessment of R-loop formation and replication stress.
  • Evaluation of S-adenosylmethionine (SAM) repletion effects.
  • Investigation of p53's transcriptional control over metabolic genes, including Slc43a2.
  • Analysis of clinical data to support findings.

Main Results:

  • p53 preserves genomic integrity by ensuring adequate levels of the methyl donor S-adenosylmethionine (SAM).
  • In p53-deficient cells, DNA methylation perturbations lead to heterochromatin derepression, loss of H3K9 methylation, and increased satellite RNA, causing replication stress and chromosomal aberrations.
  • Inadequate SAM levels in p53-deficient cells hinder the response to perturbations; exogenous SAM reintroduction represses satellite elements and restores stress tolerance.
  • p53 transcriptionally regulates genes in one-carbon metabolism, including the methionine transporter Slc43a2, crucial for SAM synthesis.

Conclusions:

  • The tumor suppressor p53 is essential for maintaining genomic stability by controlling SAM levels through transcriptional regulation of metabolic genes.
  • p53 deficiency results in epigenetic alterations and genomic instability linked to insufficient SAM, which can be rescued by SAM repletion.
  • These findings highlight the critical role of p53-mediated metabolism in preventing R-loop-associated genomic instability in cancer.