Related Experiment Video

Updated: Aug 9, 2026

Imaging Replicative Domains in Ultrastructurally Preserved Chromatin by Electron Tomography
14:56

Imaging Replicative Domains in Ultrastructurally Preserved Chromatin by Electron Tomography

Published on: May 20, 2022

Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around

O Llorca1, A Rivera-Calzada, J Grantham

  • 1The Institute of Cancer Research, Cancer Research UK, Center for Cell and Molecular Biology, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.

Oncogene
|June 19, 2003
PubMed

Insights

The ataxia telangiectasia mutated (ATM) protein kinase, crucial for DNA damage response, was visualized using electron microscopy. Structural analysis reveals ATM

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • The ataxia telangiectasia mutated (ATM) gene is a human tumor suppressor.
  • ATM protein kinase regulates cell cycle checkpoints and is vital for DNA repair.
  • Defects in ATM cause ataxia-telangiectasia, a syndrome linked to neurodegeneration and cancer predisposition.

Purpose of the Study:

  • To elucidate the structural basis of ATM protein kinase's interaction with DNA.
  • To understand the conformational changes in ATM upon DNA binding.

Main Methods:

  • Single-particle electron microscopy was used to observe purified human ATM protein and its complexes with DNA.
  • Three-dimensional reconstructions of ATM-DNA and ATM-DNA-avidin bound complexes were obtained.

Main Results:

  • The study visualized purified human ATM protein and its DNA-bound complexes.
  • Three-dimensional reconstructions revealed ATM comprises a head and an arm domain.
  • DNA binding induced a significant conformational change in ATM's arm domain, suggesting a DNA-clamping mechanism.

Conclusions:

  • ATM interacts with DNA through a conformational mechanism involving its arm domain.
  • These findings provide structural insights into ATM's role in DNA damage sensing and cell cycle regulation.

More Related Videos

Deciphering Molecular Mechanism of Histone Assembly by DNA Curtain Technique06:32

Deciphering Molecular Mechanism of Histone Assembly by DNA Curtain Technique

Published on: March 9, 2022

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase07:37

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase

Published on: September 27, 2024

Related Concept Videos

The Replisome03:01

The Replisome

DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
Homologous Recombination02:31

Homologous Recombination

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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...