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Mutations01:39

Mutations

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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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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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The speed of a wave depends on the characteristics of the medium. For example, in the case of a guitar, the strings vibrate to produce the sound. The speed of the waves on the strings and the wavelength determine the frequency of the sound produced. The strings on a guitar have different thicknesses but may be made of similar material. They have different linear densities, and the linear density is defined as the mass per length.
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Related Experiment Video

Updated: Feb 11, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
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SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation.

Eddy Sanchai Thientosapol1,2, Daniel Bosnjak1,2, Timothy Durack1,2

  • 1Centenary Institute, Camperdown NSW 2050, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|April 20, 2018
PubMed
Summary
This summary is machine-generated.

Scientists found that restricting nucleotide supply enhances antibody gene mutation. Inactivating SAMHD1 in B cells increased mutations but also virus susceptibility, revealing repurposed antiviral defenses in antibody hypermutation.

Keywords:
B cellsDNA repairdNTPsdeaminationmutation

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Activation-induced deaminase (AID) drives Ig gene hypermutation by creating uracil lesions.
  • DNA repair pathways and translesion polymerases exacerbate mutations initiated by AID.
  • Reduced deoxynucleotide triphosphate (dNTP) levels in G1 phase, an antiviral mechanism, may influence hypermutation.

Purpose of the Study:

  • To investigate the role of SAMHD1, a dNTPase, in regulating dNTP pools during B cell activation.
  • To determine if restricting dNTP supply by SAMHD1 enhances AID-mediated hypermutation.
  • To explore the connection between antiviral dNTP starvation and Ig hypermutation evolution.

Main Methods:

  • CRISPR-Cas9 inactivation of SAMHD1 in germinal center B cells.
  • Analysis of Ig gene mutation profiles, including transition and transversion mutations.
  • Assessment of B cell susceptibility to viral infection.

Main Results:

  • SAMHD1 inactivation in B cells led to increased susceptibility to viral infection.
  • Inactivation of SAMHD1 increased transition mutations at C:G base pairs.
  • A substantial decrease in transversion mutations at A:T and C:G base pairs was observed after SAMHD1 inactivation.

Conclusions:

  • SAMHD1's restriction of dNTP supply potentiates AID mutagenicity during Ig gene hypermutation.
  • The evolution of Ig hypermutation likely involved repurposing of innate antiviral strategies, specifically dNTP starvation.
  • Understanding this interplay offers insights into B cell immunity and mutation processes.