Related Experiment Video
Updated: Sep 28, 2025
08:40
Determination of S-Phase Duration Using 5-Ethynyl-2'-deoxyuridine Incorporation in Saccharomyces cerevisiae
Published on: October 21, 2022
1.6K
Genetic instability from a single S phase after whole-genome duplication
Simon Gemble1, René Wardenaar2, Kristina Keuper3
1Institut Curie, PSL Research University, CNRS, UMR144, Biology of Centrosomes and Genetic Instability Laboratory, Paris, France. simon.gemble@curie.fr.
Nature
|March 31, 2022
Summary
Tetraploidy, or whole-genome duplication, causes significant DNA damage and replication errors in human cells. This genetic instability during the first interphase promotes abnormal karyotypes and may drive cancer development.
Area of Science:
- Cell Biology
- Genetics
- Cancer Research
Background:
- Stable diploid karyotypes are essential for animal health.
- Whole-genome duplication (tetraploidy) is linked to genetic instability and human cancers.
- Tetraploidy fuels chromosome instability via abnormal mitosis, but its immediate interphase consequences are unknown.
Purpose of the Study:
- To investigate the immediate consequences of tetraploidy in the first interphase of human cells.
- To understand how whole-genome duplication affects DNA replication fidelity and karyotype stability.
Main Methods:
- Induction of tetraploidy in human cells.
- DNA combing and single-cell sequencing to analyze DNA replication dynamics.
- Analysis of DNA damage and protein availability during the G1/S transition.
Main Results:
- Tetraploid human cells exhibit high rates of DNA damage during the first S phase.
- DNA replication dynamics are perturbed, leading to under- and over-replicated regions.
- Protein shortages during the G1/S transition impair DNA replication fidelity.
Conclusions:
- Unscheduled tetraploid cells acquire highly abnormal karyotypes within a single interphase.
- These findings explain the genetic instability promoting tumorigenesis after tetraploidization.
- Defects in DNA replication fidelity are a key mechanism linking tetraploidy to karyotype abnormalities.
Related Concept Videos
02:37Gene Duplication and Divergence
6.6K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
6.6K
02:08Gene Conversion
10.0K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
10.0K
02:38S-Cdk Initiates DNA Replication
4.9K
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...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.9K
02:46Genome Copying Errors
4.5K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.5K
02:04Fixing Double-strand Breaks
13.0K
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...
13.0K
02:21Cancers Originate from Somatic Mutations in a Single Cell
13.2K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
13.2K