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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

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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.
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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...
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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.
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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...
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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?

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|August 26, 2022
PubMed
Summary

Synthetic lethality strategies targeting chromatin remodeling proteins offer new cancer treatment avenues. Combining epigenetic enzymes and kinases can improve efficacy and reduce toxicity for better patient outcomes.

Keywords:
chromatin kinaselysine acetylaselysine deacetylaselysine demethylaselysine methylase

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Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Synthetic lethality is a promising strategy for targeted cancer therapy.
  • Chromatin remodeling is crucial for tumor biology and represents a druggable target.
  • Epigenetic modifiers and chromatin kinases are key regulators of chromatin organization.

Purpose of the Study:

  • To explore synthetic lethality strategies by combining epigenetic enzymes and chromatin kinases.
  • To identify novel therapeutic targets and improve existing cancer treatments.
  • To enhance the effectiveness and reduce the toxicity of DNA-damage-based therapies.

Main Methods:

  • Investigating the roles of epigenetic enzymes (histone acetylases, deacetylases, methylases, demethylases) and chromatin kinases (e.g., Aurora kinases, ATM, ATR) in cancer.
  • Analyzing the convergence of these proteins on chromatin regulation.
  • Evaluating combined targeting approaches in synthetic lethality frameworks.

Main Results:

  • Epigenetic enzymes and chromatin kinases are druggable targets involved in chromatin dynamics.
  • Combined targeting can exploit synthetic lethality in tumor cells.
  • This approach can sensitize cancer cells to DNA-damage treatments.

Conclusions:

  • Combined targeting of epigenetic enzymes and kinases via synthetic lethality can enhance cancer treatment specificity.
  • This strategy may reduce treatment toxicity and tumor resistance.
  • Improved immunogenicity and survival are potential benefits for patients.