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Related Concept Videos

Meiosis vs. Mitosis02:57

Meiosis vs. Mitosis

Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
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...
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Nondisjunction01:29

Nondisjunction

During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
Nondisjunction01:21

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...

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Related Experiment Video

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

DNA breaks and chromosome pulverization from errors in mitosis.

Karen Crasta1, Neil J Ganem, Regina Dagher

  • 1Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.

Nature
|January 20, 2012
PubMed
Summary

Errors in cell division create micronuclei, leading to DNA damage and fragmentation. This process may explain chromosome chaos in cancer and developmental disorders.

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Area of Science:

  • Cell Biology
  • Genetics
  • Cancer Research

Background:

  • The role of whole-chromosome aneuploidy in cancer development remains unclear due to limited understanding of its mechanisms.
  • Mitotic errors, specifically chromosome segregation errors, are implicated in aneuploidy but the precise pathways are not fully elucidated.

Purpose of the Study:

  • To investigate the mechanisms by which mitotic errors lead to DNA damage and potential genomic instability.
  • To explore the fate of chromosomes mis-segregated during mitosis and their contribution to tumorigenesis.

Main Methods:

  • Tracking the formation and fate of micronuclei generated from lagging chromosomes during mitosis.
  • Analyzing DNA replication, damage, and fragmentation within micronuclei over several cell generations.

Main Results:

  • Mitotic errors generate whole-chromosome micronuclei containing lagging chromosomes.
  • These micronuclei exhibit defective and asynchronous DNA replication, leading to DNA damage and fragmentation.
  • Micronuclei can persist, potentially integrating fragmented chromosomes into daughter nuclei, or undergo pulverization.

Conclusions:

  • Chromosome segregation errors generate DNA breaks through micronuclei formation and subsequent fragmentation.
  • This mechanism provides a potential explanation for chromothripsis observed in cancer and developmental disorders.
  • Micronuclei-induced genomic instability may contribute to tumorigenesis.