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Related Concept Videos

Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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...
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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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Visualization of DNA Repair Proteins Interaction by Immunofluorescence
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Published on: June 26, 2020

Full-length hdmX transcripts decrease following genotoxic stress.

M Markey1, S J Berberich

  • 1Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA.

Oncogene
|August 20, 2008
PubMed
Summary

DNA-damaging agents decrease human mdmX (hdmX) mRNA levels, independent of p53. This reduction in hdmX transcripts is linked to altered splicing and microRNA regulation, impacting HdmX protein levels following genotoxic stress.

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Published on: June 6, 2017

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Previous research indicated constitutive transcription of the mdmX gene, with MdmX protein activity regulated by cellular localization and Mdm2-mediated degradation.
  • The role of DNA damage in regulating mdmX mRNA levels remained largely unexplored.

Purpose of the Study:

  • To investigate the impact of DNA-damaging agents on human mdmX (hdmX) mRNA levels.
  • To elucidate the mechanisms underlying changes in hdmX mRNA following genotoxic stress.

Main Methods:

  • Treatment of various human cell lines (including HCT116 colon cancer cells and isogenic p53(-/-) cells) and primary human diploid fibroblasts with DNA-damaging agents.
  • Quantification of hdmX mRNA levels and analysis of promoter activity.
  • Investigation of mRNA splicing, transcript stability, and potential microRNA involvement (miR-34a).

Main Results:

  • DNA-damaging agents reproducibly decreased hdmX mRNA levels across multiple human cell types.
  • This repression was observed in both p53-proficient and p53-deficient cells, indicating a p53-independent mechanism.
  • Reduced hdmX mRNA levels correlated with decreased HdmX protein and were partly attributed to altered mRNA splicing and transcript destabilization, potentially involving miR-34a.

Conclusions:

  • Genotoxic stress induces a significant reduction in hdmX mRNA levels through p53-independent pathways.
  • Mechanisms include altered mRNA splicing and transcript destabilization, potentially mediated by microRNAs like miR-34a.
  • These findings reveal novel regulatory mechanisms controlling hdmX mRNA levels under DNA damage conditions.