Related Experiment Video

Updated: May 10, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

DNA repair choice defines a common pathway for recruitment of chromatin regulators

Gwendolyn Bennett1, Manolis Papamichos-Chronakis, Craig L Peterson

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01606, USA.

Nature Communications
|July 2, 2013
PubMed

Insights

Efficient DNA repair requires chromatin regulators, but how they are recruited to DNA breaks is unclear. This study reveals their recruitment is controlled by homologous recombination, not H2A.X phosphorylation, and influenced by cell cycle stage.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA double-strand breaks (DSBs) threaten genome stability.
  • Chromatin regulators are crucial for the DNA damage response (DDR).
  • Mechanisms controlling chromatin regulator recruitment to DNA lesions are largely unknown.

Purpose of the Study:

  • To elucidate the mechanisms governing the recruitment of chromatin regulators to DNA double-strand breaks.
  • To investigate the interplay between DNA repair pathways and chromatin regulator recruitment.
  • To determine the role of H2A.X phosphorylation and cell cycle position in this process.

Main Methods:

  • Investigated the recruitment dynamics of key chromatin-modulating complexes (INO80, SWR-C, NuA4, SWI/SNF, RSC) to DNA lesions.
  • Assessed the influence of non-homologous end-joining (NHEJ) and homologous recombination (HR) pathways on recruitment.
  • Monitored H2A.X phosphorylation levels in correlation with chromatin regulator presence.
  • Analyzed the impact of cell cycle progression on DNA repair pathway choice and regulator recruitment.

Main Results:

  • Recruitment of INO80, SWR-C, NuA4, SWI/SNF, and RSC enzymes to DSBs is inhibited by the NHEJ machinery.
  • Chromatin regulator recruitment is actively controlled by early steps of homologous recombination.
  • H2A.X phosphorylation plays no significant role in recruiting chromatin regulators; their arrival coincides with reduced H2A.X phosphorylation.
  • Cell cycle position critically influences DNA repair pathway selection.

Conclusions:

  • Chromatin regulator recruitment to DNA breaks is tightly coupled to homologous recombination.
  • The cell cycle dictates DNA repair pathway choice, impacting chromatin regulator dynamics.
  • These findings reveal a novel regulatory mechanism for DNA repair pathway coordination.

More Related Videos

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

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

Related Concept Videos

Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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 Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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...
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...