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Related Concept Videos

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...
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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Pre-mRNA processing factors meet the DNA damage response.

Alessandra Montecucco1, Giuseppe Biamonti

  • 1Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche Pavia, Italy.

Frontiers in Genetics
|June 14, 2013
PubMed
Summary

Chromosome fragility increases during transcription due to RNA processing. Proper RNA maturation is crucial for maintaining genome stability and preventing DNA damage, especially in cancer.

Keywords:
DNA damage responseRNA binding proteinscheckpoint kinasespre-mRNA processingsplicing

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Chromosomes are inherently fragile and prone to DNA breakage, exacerbated by DNA replication.
  • Transcription, particularly RNA polymerase II (RNAPII) activity, also increases chromosome fragility.
  • RNA maturation involves multiple processing steps, recruitment of proteins, and transport, all influenced by RNAPII.

Purpose of the Study:

  • To review the role of pre-mRNA processing factors in the cellular response to DNA damage.
  • To explore the connection between RNA metabolism and genome stability maintenance.
  • To highlight transcription as a potential source of DNA damage in cancer.

Main Methods:

  • Literature review of recent findings and high-throughput screenings.
  • Analysis of studies implicating RNA metabolism factors in DNA damage checkpoints.
  • Examination of evidence linking RNA processing defects to genome instability markers like γH2AX foci.

Main Results:

  • Coordination of RNA maturation steps is essential for genome stability; disruptions can lead to DNA damage.
  • Factors involved in RNA metabolism are targeted by DNA damage checkpoint kinases ATM and ATR.
  • Inactivation of RNA processing factors results in accumulation of γH2AX foci, indicating DNA damage.

Conclusions:

  • A complex network linking DNA repair and RNA metabolism is emerging.
  • Pre-mRNA processing factors play a critical role in the cell's response to DNA damage.
  • Dysregulation of RNA metabolism contributes to genome instability and may be a significant factor in cancer development.