Related Experiment Video

Updated: Jul 4, 2026

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
09:46

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP

Published on: January 24, 2025

Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

Ji-Young Hwang1, Stephanie Smith, Audrey Ceschia

  • 1Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892 USA.

DNA Repair
|July 1, 2008
PubMed

Insights

The Smc5-Smc6 complex suppresses chromosome translocations, a type of gross chromosomal rearrangement (GCR), by preventing DNA damage at repetitive sequences. This discovery reveals a new mechanism for maintaining genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Chromosome translocations alter genetic information and are frequently observed in tumors, suggesting a role in tumorigenesis.
  • The precise mechanisms by which translocations are suppressed or produced remain poorly understood.
  • Gross chromosomal rearrangements (GCRs) are significant contributors to genomic instability.

Purpose of the Study:

  • To investigate the role of the Smc5-Smc6 complex in suppressing translocations and other GCRs.
  • To elucidate the mechanisms underlying translocation formation and suppression, particularly in relation to DNA damage at repetitive sequences.

Main Methods:

  • Analysis of a smc6-9 mutant strain exhibiting increased translocation GCRs.
  • Characterization of translocation properties, including dependence on break-induced replication (BIR) and independence from non-homologous end joining (NHEJ).
  • Assessment of translocation incidence near repetitive sequences (delta sequences, ARS, tRNA genes, telomeres).
  • Examination of synergistic effects of the smc6-9 mutation with DNA damage checkpoint deficiencies.

Main Results:

  • The smc6-9 mutation significantly increased translocation class GCRs.
  • Translocations in smc6-9 are non-reciprocal, dependent on BIR, and independent of NHEJ.
  • High translocation frequency near repetitive sequences in smc6-9 suggests Smc5-Smc6 suppresses translocations by reducing DNA damage at these sites.
  • Synergistic enhancement of translocations in checkpoint-defective strains points to a novel GCR suppression pathway involving Smc5-Smc6.

Conclusions:

  • The Smc5-Smc6 complex plays a critical role in suppressing translocations, a specific class of GCRs.
  • Smc5-Smc6 functions by mitigating DNA damage at repetitive genomic sequences.
  • Smc5-Smc6 represents a newly identified pathway crucial for preventing gross chromosomal rearrangement formation.

More Related Videos

Genetic Screen for Identification of Multicopy Suppressors in Schizosaccharomyces pombe13:22

Genetic Screen for Identification of Multicopy Suppressors in Schizosaccharomyces pombe

Published on: September 13, 2022

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe07:55

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe

Published on: March 7, 2019

Related Concept Videos

Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
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...
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...
Chromosome Replication02:31

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin of...