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Related Concept Videos

Overview of DNA Repair02:25

Overview of DNA Repair

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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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Proteomics01:33

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A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
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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 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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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

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Current proteomics methods applicable to dissecting the DNA damage response.

Monita Muralidharan1,2, Nevan J Krogan1,2, Mehdi Bouhaddou1,2,3,4

  • 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.

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Summary
This summary is machine-generated.

Proteomics techniques like mass spectrometry are revolutionizing DNA damage response (DDR) research. These methods globally analyze protein changes, PTMs, localization, and interactions, aiding genome stability studies.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • The DNA damage response (DDR) is crucial for maintaining genome stability through coordinated proteomic regulation.
  • Traditional DDR studies focused on individual proteins, limiting a holistic understanding.
  • Advances in proteomics offer unprecedented capabilities to study DDR comprehensively.

Purpose of the Study:

  • To review cutting-edge functional and structural proteomics techniques applied to DDR research.
  • To highlight how these methods interrogate proteomic changes regulating DNA repair.
  • To emphasize the role of proteomics in understanding genome stability.

Main Methods:

  • Mass spectrometry (MS)-based proteomics for global quantification of protein abundance, PTMs, and localization.
  • MS-based techniques for analyzing protein-protein interactions (PPIs).
  • Structural proteomics approaches like crosslinking MS (XL-MS), H/DX-MS, and Native MS (nMS) for structural insights.

Main Results:

  • Proteomics enables global analysis of proteomic changes during DDR.
  • Structural proteomics provides complementary data for integrated structural modeling of DDR complexes.
  • These techniques offer a deeper understanding of DDR regulation.

Conclusions:

  • Functional and structural proteomics are powerful tools for dissecting the DDR.
  • These advanced methods are essential for investigating the complex proteomic landscape of DNA repair.
  • Continued development of proteomics will advance our understanding of genome stability.