Related Experiment Video

Updated: Jun 7, 2025

Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization
17:14

Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization

Published on: December 10, 2012

13.9K

Chromosomal rearrangements associated with SMC5/6 deficiency in DNA replication

Yoshiharu Kusano1,2, Yasuha Kinugasa3, Satoshi Tashiro3

  • 1Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|November 14, 2024
PubMed

Insights

Incomplete DNA replication, particularly at fragile sites, causes chromosome bridges and breaks. This leads to complex rearrangements and genomic instability, potentially driving human cancers.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Stable genome maintenance requires complete DNA replication before chromosome segregation.
  • Replication stress can cause persistent DNA synthesis beyond S phase, especially in difficult-to-replicate genomic regions.

Purpose of the Study:

  • To investigate how incomplete replication, specifically due to SMC5/6 deficiency, affects sister chromatid disjunction.
  • To characterize the resulting chromosome rearrangements and their contribution to genomic instability.

Main Methods:

  • Studied the effects of SMC5/6 deficiency on DNA replication and chromosome segregation.
  • Analyzed cytological features of mitotic chromosomes, including anaphase bridges and gaps.
  • Investigated chromosome rearrangements, micronucleation, and fragmentation using cytogenetic methods.

Main Results:

  • SMC5/6 deficiency impairs sister chromatid disjunction at difficult-to-replicate regions and common fragile sites.
  • Incomplete replication leads to anaphase bridges, telomere loss, micronucleation, and chromosome fragmentation.
  • Telomere loss promotes chromosome fusions, generating complex rearrangements like dicentric chromosomes and chromothripsis.

Conclusions:

  • Incomplete replication is a significant driver of complex chromosomal rearrangements.
  • These rearrangements, facilitated by breakage-fusion-bridge cycles and chromothripsis, contribute to genomic instability.
  • The findings suggest a link between replication stress, chromosomal instability, and human cancers.
Keywords:
SMC5/6anaphase bridgebreakage‐fusion‐bridge cyclechromothripsiscommon fragile sites

More Related Videos

Chromosome Preparation From Cultured Cells07:42

Chromosome Preparation From Cultured Cells

Published on: January 28, 2014

81.1K
Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae09:40

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae

Published on: September 23, 2011

14.6K

Related Concept Videos

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...
5.9K
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,...
5.8K
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...
12.3K
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...
50.2K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K
Mismatch Repair01:36

Mismatch Repair

Overview
39.9K