Related Experiment Video
Updated: Jun 23, 2026
07:55
Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
Published on: September 11, 2022
Cohesin activity accelerates the homology search
Biorxiv : the Preprint Server for Biology
|June 22, 2026
Summary
Cohesin dramatically speeds up DNA double-strand break (DSB) repair by transforming the homology search into an efficient 1D scan. This process is enhanced by cohesin anchoring and loop extrusion within topologically associating domains (TADs).
Area of Science:
- Molecular Biology
- Genetics
- Biophysics
Background:
- Homologous recombination (HR) is crucial for maintaining genome integrity by repairing DNA double-strand breaks (DSBs) in post-replicative cells.
- The homology search, where a DSB finds its repair template, is a critical and complex stage of HR.
- Chromatin architecture, particularly the role of cohesin, is implicated in regulating DNA repair processes.
Purpose of the Study:
- To model the mammalian homology search during HR repair using molecular dynamics simulations.
- To investigate the specific role of the chromatin factor cohesin in accelerating the homology search.
- To elucidate how cohesin's structural functions, like loop extrusion, influence DSB repair efficiency.
Main Methods:
- Utilized molecular dynamics simulations to model the homology search process in mammalian cells.
- Focused on the interactions between DNA double-strand breaks (DSBs) and cohesin complexes.
- Analyzed the impact of cohesin-mediated chromatin looping and TAD structures on search dynamics.
Main Results:
- Simulations confirmed experimental observations regarding DSB-mediated locus interrogation and chromatin interactions.
- Cohesin-mediated loop extrusion significantly accelerates the homology search.
- Anchoring loop-extruding cohesin at DSB sites and cohesive cohesin clamps further enhance search efficiency.
- The acceleration effect of cohesin scales linearly with TAD size, being more pronounced in larger TADs.
- Distinct roles were identified for chromatin loops on the broken and sister chromatids in facilitating contact and scanning.
Conclusions:
- Cohesin plays a pivotal role in optimizing the homology search, transforming it from a 3D diffusion process to a rapid 1D scanning mechanism.
- The coordinated action of loop-extruding and cohesive cohesin is essential for efficient DSB repair.
- Understanding cohesin's function in HR provides insights into genome stability maintenance and potential therapeutic strategies.
Related Concept Videos
02:20Cohesins
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...
02:20Cohesins
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...
02:31Homologous 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...
02:31Homologous 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...
01:30Crossing Over
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...
01:34Crossing Over
Unlike mitosis, meiosis aims for genetic diversity in its creation of haploid gametes. Dividing germ cells first begin this process in prophase I, where each chromosome—replicated in S phase—is now composed of two sister chromatids (identical copies) joined centrally.
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...