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Fixing Double-strand Breaks

Fixing Double-strand Breaks

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...

Fixing Double-strand Breaks

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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...

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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

Nucleotide Excision Repair

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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...

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Updated: May 22, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

DNA breakage drives nuclear search.

Grzegorz Ira¹, Philip J Hastings

¹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. gira@bcm.edu

Nature Cell Biology

|May 4, 2012

Summary

Broken chromosomes actively move within the cell nucleus, searching for a homologous template to repair DNA double-strand breaks. This search requires specific enzymes and DNA damage checkpoint proteins.

Area of Science:

Molecular Biology
Cell Biology
Genetics

Background:

DNA double-strand breaks (DSBs) are severe DNA lesions.
Homologous recombination (HR) is a major DSB repair pathway.
The search for a homologous template during HR is poorly understood.

Purpose of the Study:

To investigate the physical movement of broken chromosomes during DNA repair.
To identify factors influencing the search for a homologous template.

Main Methods:

Live-cell imaging of DNA breaks.
Analysis of chromosome dynamics.
Genetic and biochemical assays.

Main Results:

Broken chromosomes exhibit increased mobility within the nucleus.

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Visualization of DNA Repair Proteins Interaction by Immunofluorescence

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This mobility allows exploration of larger nuclear volumes.

Break movement depends on DNA resection, recombination enzymes, and checkpoint proteins.

Conclusions:

Chromosome mobility is a key feature of homologous template search in DNA repair.
This active search mechanism ensures efficient and accurate repair of DNA double-strand breaks.