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Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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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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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.
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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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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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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
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When RNA damage induces DNA breaks.

Ivan Mikicic1, Petra Beli2

  • 1Institute of Molecular Biology (IMB), 55128 Mainz, Germany.

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Cells possess a novel nuclear RNA damage repair pathway. RNA alkylation unexpectedly triggers R-loops and DNA breaks, revealing new cellular defense mechanisms against RNA damage.

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R-loopsRNATHOCYTHDC1alkylationbase damage

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Alkylated messenger RNAs (mRNAs) are recognized to activate ribosome quality control mechanisms within the cytoplasm.
  • The cellular response to damaged RNAs, particularly within the nucleus, remains less understood.

Purpose of the Study:

  • To investigate the cellular mechanisms for repairing damaged RNAs in the nucleus.
  • To explore the consequences of RNA alkylation on nuclear processes and genome integrity.

Main Methods:

  • Utilized molecular biology techniques to study RNA damage and repair pathways.
  • Employed genetic and cellular assays to analyze the effects of RNA alkylation.

Main Results:

  • Discovered a previously unknown pathway for RNA damage repair operating in the nucleus.
  • Demonstrated that RNA alkylation can unexpectedly induce the formation of R-loops (RNA-DNA hybrids).
  • Observed that RNA alkylation leads to the induction of DNA breaks.

Conclusions:

  • RNA alkylation triggers a novel nuclear RNA repair pathway.
  • RNA alkylation poses a significant threat to genome stability by inducing R-loops and DNA breaks.