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Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
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Base Excision Repair01:54

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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
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Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
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Bioorthogonal oncometabolite ligation.

Chloe A Briney1, Susana Najera1, Jordan L Meier1

  • 1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States.

Methods in Enzymology
|June 4, 2019
PubMed
Summary
This summary is machine-generated.

Researchers developed a new bioorthogonal method to detect fumarate, a key metabolite in cancer. This technique aids in understanding cancer metabolism and diagnosing conditions like hereditary leiomyomatosis and renal cell cancer (HLRCC).

Keywords:
BioorthogonalBioorthogonal oncometabolite ligation: HLRCCClick chemistryCycloadditionFluorogenicFumarateFumarate hydrataseHereditary cancerProfilingSensorTetrazole

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Area of Science:

  • Biochemistry
  • Oncology
  • Metabolomics

Background:

  • Dysregulated cellular metabolism is a recognized hallmark of cancer.
  • Accurate profiling of metabolic activity is crucial for cancer diagnosis and biological understanding.
  • Aberrant metabolism, particularly involving the TCA cycle, is increasingly linked to tumor development.

Purpose of the Study:

  • To develop a novel bioorthogonal ligation method for fluorescent detection of the TCA cycle oncometabolite fumarate.
  • To enable facile measurement of fumarate hydratase (FH) activity in biological samples.
  • To detect metabolic disruptions associated with genetic cancer syndromes, such as hereditary leiomyomatosis and renal cell cancer (HLRCC).

Main Methods:

  • Utilized bioorthogonal ligation chemistry for specific detection of fumarate.
  • Developed a fluorescent probe for fumarate detection.
  • Applied the method to measure FH activity in cell and tissue samples.

Main Results:

  • Successfully demonstrated fluorescent detection of fumarate using the bioorthogonal ligation.
  • Enabled facile measurement of fumarate hydratase activity.
  • Showed utility in detecting metabolic disruptions characteristic of HLRCC.

Conclusions:

  • The developed method provides sensitive fumarate hydratase activity profiling.
  • This technique offers a foundation for future diagnostic detection and imaging of cancer metabolism.
  • The approach aids in understanding the role of metabolic aberrations in cancer biology.