Related Experiment Video

Updated: Feb 11, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
08:17

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

3.0K

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

Activation-induced deaminase (AID) initiates hypermutation of Ig genes in activated B cells by converting C:G into U:G base pairs. G1-phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G1 phase to inhibit viral replication. To derestrict G1-phase dNTP supply, we CRISPR-inactivated SAMHD1 (which degrades dNTPs) in germinal center B cells. Samhd1 inactivation increased B cell virus susceptibility, increased transition mutations at C:G base pairs, and substantially decreased transversion mutations at A:T and C:G base pairs in both strands. We conclude that SAMHD1's restriction of dNTP supply enhances AID's mutagenicity and that the evolution of Ig hypermutation included the repurposing of antiviral mechanisms based on dNTP starvation.

Keywords:
B cellsDNA repairdNTPsdeaminationmutation

More Related Videos

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches09:35

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches

Published on: April 20, 2021

7.3K
Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes08:12

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

20.4K

Related Concept Videos

Mutations01:39

Mutations

Overview
94.6K
Mutations01:35

Mutations

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.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.7K
Viral Mutations00:36

Viral Mutations

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...
40.0K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

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...
18.9K
Speed of a Transverse Wave01:13

Speed of a Transverse Wave

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.
One of the key properties of any wave is the wave speed. Light...
4.0K
Deformations in a Transverse Cross Section01:21

Deformations in a Transverse Cross Section

When a material is subjected to uniaxial stress, it elongates or contracts in the direction of the applied force, and also undergoes changes in the perpendicular directions. This behavior is crucial for understanding how materials behave under stress and is governed by mechanical properties such as Poisson's ratio v, which measures the ratio of transverse strain to axial strain.
As the material stretches, it expands or contracts in orthogonal directions to the load. This phenomenon varies...
653