Related Experiment Video

Updated: Jun 7, 2026

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

ATM modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot

Jiying Sun1, Yukako Oma, Masahiko Harata

  • 1Department of Cellular Biology, RIRBM, Hiroshima University, Hiroshima, Japan.

Plos One
|November 5, 2010
PubMed

Insights

Ataxia-telangiectasia mutated (ATM) protein deficiency increases DNA recombination protein binding at translocation sites, potentially leading to secondary leukemia. ATM may prevent translocations by limiting this binding.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Chromosome translocations are key events in malignant transformation, often induced by DNA damaging agents.
  • Loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, elevates chromosome translocation incidence.
  • The mechanisms by which ATM prevents translocations, particularly those involving the MLL gene in secondary leukemias, remain largely unknown.

Purpose of the Study:

  • To elucidate the role of ATM in preventing chromosome translocations, specifically focusing on the 11q23 breakpoint hotspot after etoposide exposure.
  • To investigate the impact of ATM deficiency on the recruitment of DNA repair proteins at translocation breakpoints.

Main Methods:

  • Utilized etoposide exposure in an experimental model to induce DNA damage and chromosome translocations.
  • Assessed the binding of DNA recombination and repair proteins, including RAD51, RPA, and INO80, to the 11q23 translocation breakpoint hotspot in ATM-deficient cells.
  • Compared protein binding levels in ATM-deficient versus wild-type cells.

Main Results:

  • ATM deficiency led to excessive binding of the DNA recombination protein RAD51 at the 11q23 translocation breakpoint hotspot following etoposide treatment.
  • Increased binding of Replication protein A (RPA) and the chromatin remodeler INO80 was also observed in ATM-deficient cells at the hotspot.
  • These proteins are known to facilitate RAD51 loading onto damaged DNA.

Conclusions:

  • ATM plays a crucial role in averting chromosome translocations beyond its known DNA damage signaling function.
  • ATM may prevent translocations by inhibiting the excessive loading of recombinational repair proteins, such as RAD51, onto critical breakpoint regions.
  • These findings offer new insights into the mechanisms underlying secondary leukemias and potential therapeutic strategies.

More Related Videos

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Related Concept Videos

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...
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...
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...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...