Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.1K
Homologous Recombination02:31

Homologous Recombination

50.6K
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...
50.6K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

12.6K
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...
12.6K
DNA Helicases00:55

DNA Helicases

21.4K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.4K
Maxam-Gilbert Sequencing01:05

Maxam-Gilbert Sequencing

11.2K
In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
Challenges of the Maxam-Gilbert Method
The...
11.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Transition Metal Activation Reframes SAMHD1 Regulation.

ACS chemical biology·2026
Same author

The ITCC-P4 PDX Platform Enables Preclinical Testing of Pediatric Cancers.

Cancer research·2026
Same author

Transition metal activation reframes SAMHD1 regulation.

bioRxiv : the preprint server for biology·2026
Same author

Tunable Cell Surface Proximity Labeling via Photocatalytic and Enzymatic Activation of Fast Bioorthogonal Chemistry.

Journal of the American Chemical Society·2026
Same author

Discovery of Potent and Brain-Penetrant Inverse Agonists for GPR61, an Orphan G Protein-Coupled Receptor.

Journal of medicinal chemistry·2026
Same author

Protein cleaver: an interactive web interface for <i>in silico</i> prediction and systematic annotation of protein digestion-derived peptides.

Frontiers in bioinformatics·2025

Related Experiment Video

Updated: Jul 11, 2025

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

2.4K

Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.

Benjamin Orris1, Min Woo Sung2, Shridhar Bhat1

  • 1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine 725 North Wolfe Street Baltimore, MD 21205, USA.

Nucleic Acids Research
|November 6, 2023
PubMed
Summary

Deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) binds guanine in single-stranded DNA and RNA. Guanine binding induces SAMHD1 dimerization or tetramerization, affecting its enzymatic activity.

More Related Videos

Chemical Dimerization-Induced Protein Condensates on Telomeres
08:52

Chemical Dimerization-Induced Protein Condensates on Telomeres

Published on: April 12, 2021

3.2K
Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
09:43

Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

2.4K

Related Experiment Videos

Last Updated: Jul 11, 2025

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

2.4K
Chemical Dimerization-Induced Protein Condensates on Telomeres
08:52

Chemical Dimerization-Induced Protein Condensates on Telomeres

Published on: April 12, 2021

3.2K
Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
09:43

Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells

Published on: June 13, 2021

2.4K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) regulates cellular dNTP levels.
  • SAMHD1 interacts with DNA replication forks, DNA repair foci, ssRNA, and telomeres, requiring nucleic acid binding.
  • The oligomeric state of SAMHD1 may modulate its functions.

Purpose of the Study:

  • To investigate how SAMHD1 binds to nucleic acids.
  • To determine the structural basis for SAMHD1-nucleic acid interactions.
  • To understand how nucleic acid binding affects SAMHD1's oligomeric state and enzymatic activity.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine structures.
  • Biochemical assays to study enzyme activity and nucleic acid binding.

Main Results:

  • SAMHD1 uses its guanine-specific A1 activator site to bind guanine nucleotides in ssDNA and ssRNA.
  • A single guanine induces SAMHD1 dimerization, while two or more guanines spaced by ~20 nucleotides induce tetramerization.
  • Cryo-EM structure of ssRNA-bound tetrameric SAMHD1 reveals ssRNA bridging two SAMHD1 dimers.
  • The ssRNA-bound tetramer is inactive for dNTPase and RNase activity.

Conclusions:

  • Nucleic acid binding, specifically to guanine, is a key regulator of SAMHD1's oligomeric state.
  • The observed conformational changes and inactivation of the tetramer upon ssRNA binding provide insights into SAMHD1 regulation.
  • This study elucidates a novel mechanism for SAMHD1 regulation through guanine-dependent oligomerization and nucleic acid interaction.