The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks

Related Experiment Video

Updated: Jul 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

Katsuhiro Hanada1, Magda Budzowska, Sally L Davies

  • 1Department of Cell Biology & Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

Nature Structural & Molecular Biology
|October 16, 2007
PubMed

Insights

Mus81, a key enzyme, prevents DNA breaks during replication fork stalling. Its absence leads to chromosomal instability and impaired DNA repair, highlighting its role in maintaining genome integrity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Genome duplication relies on structure-specific endonucleases to resolve replication fork issues caused by DNA damage.
  • While studied in bacteria (e.g., RuvABC complex), the roles of these enzymes in mammalian cells are less understood.
  • Mus81 is identified as the catalytic subunit of a eukaryotic endonuclease that cleaves branched DNA structures, crucial for replication and recombination.

Purpose of the Study:

  • To investigate the mechanisms by which Mus81 maintains chromosomal stability in eukaryotic cells.
  • To elucidate the role of Mus81 in processing aberrant DNA structures arising during replication.
  • To understand how Mus81 function impacts DNA repair and prevents genomic instability.

Main Methods:

  • Investigated Mus81's role in response to replication inhibition.
  • Assessed the impact of Mus81 deficiency on DNA double-strand break formation.
  • Analyzed the recovery of stalled replication forks in the presence and absence of functional Mus81.
  • Evaluated chromosomal aberrations in Mus81-deficient cells.

Main Results:

  • Mus81 is implicated in the formation of double-strand DNA breaks when DNA replication is inhibited.
  • Cells lacking functional Mus81 exhibit attenuated recovery of stalled replication forks.
  • Absence of Mus81 leads to the emergence of chromosomal aberrations, indicating genomic instability.
  • Mus81 activity is essential for processing potentially harmful DNA structures during replication.

Conclusions:

  • Mus81 plays a critical role in maintaining chromosomal stability by resolving complex DNA structures formed during replication.
  • It acts by converting detrimental replication-associated DNA structures into intermediates that facilitate DNA repair.
  • Mus81 deficiency compromises genome integrity, leading to increased DNA breaks and chromosomal abnormalities.

More Related Videos

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase07:27

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Published on: April 29, 2010

Visualizing Single-Stranded DNA Foci in the G1 Phase of the Cell Cycle08:30

Visualizing Single-Stranded DNA Foci in the G1 Phase of the Cell Cycle

Published on: December 22, 2023

Related Concept Videos

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...
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...
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...
Fixing Double-strand Breaks02:04

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 Breaks02:04

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...
The DNA Replication Fork01:02

The DNA Replication Fork

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...