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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 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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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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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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Author Spotlight: Combining Proximity Ligand Assay with Gamma-H2AX Staining to Characterize Protein Interactions in DNA Damage Response
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Non-coding RNAs: an emerging player in DNA damage response.

Chunzhi Zhang1, Guang Peng2

  • 1Department of Radiation Oncology, Tianjin Huan Hu Hospital, Tianjin 300060, China.

Mutation Research. Reviews in Mutation Research
|March 22, 2015
PubMed
Summary

Non-coding RNAs are vital for genomic stability and cancer prevention. They interact with DNA damage response (DDR) pathways to regulate gene expression, offering potential as cancer biomarkers and therapeutic targets.

Keywords:
DNA damage responseNon-coding RNAslncRNAsmiRNAs

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Genomic stability is crucial for cell survival and preventing cancer.
  • Non-coding RNAs (ncRNAs) are increasingly recognized for their roles in cellular processes.
  • The interplay between ncRNAs and the DNA damage response (DDR) pathway is critical for genome maintenance.

Purpose of the Study:

  • To elucidate the regulatory roles of non-coding RNAs in DNA damage response pathways.
  • To highlight the mechanisms by which ncRNAs, particularly miRNAs and lncRNAs, influence DDR.
  • To explore the clinical potential of ncRNAs in cancer therapy.

Main Methods:

  • Review of existing literature on ncRNAs and DDR.
  • Analysis of regulatory mechanisms including transcriptional, post-transcriptional, and degradation levels.
  • Examination of miRNA and lncRNA functions in DNA damage sensing, signaling, repair, and apoptosis.

Main Results:

  • DNA damage induces significant alterations in ncRNA expression.
  • ncRNAs, especially miRNAs and lncRNAs, directly regulate DDR gene expression through various mechanisms.
  • MiRNAs are essential for multiple facets of the cellular DNA damage response.
  • lncRNAs employ diverse regulatory models (signal, decoy, guide, scaffold) to control DDR genes.

Conclusions:

  • Non-coding RNAs are integral components of the DNA damage response network.
  • Dysregulation of ncRNAs contributes to genomic instability and tumorigenesis.
  • ncRNAs hold promise as biomarkers and therapeutic targets for cancer treatment, particularly in conjunction with DNA-damaging agents.