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Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
07:14

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Published on: September 20, 2019

Mitotic DNA damage targets the Aurora A/TPX2 complex.

Payal Bhatia1, Mirco Menigatti, Michele Brocard

  • 1Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.

Cell Cycle (Georgetown, Tex.)
|November 25, 2010
PubMed
Summary
This summary is machine-generated.

DNA damage inhibits Aurora A kinase activity by disrupting its interaction with TPX2. This occurs through increased TPX2 degradation and reduced TPX2 mRNA translation, impacting cell cycle arrest.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • DNA damage triggers cell cycle arrest to allow for repair.
  • Aurora A (AurA) kinase is crucial for cell cycle progression.
  • Previous work linked DNA damage-induced G2 arrest to AurA inhibition.

Purpose of the Study:

  • To elucidate the mechanism of DNA damage-induced Aurora A inhibition.
  • To investigate how ionizing radiation (IR) affects AurA activity and its interaction with TPX2.

Main Methods:

  • Irradiation of cells in mitosis.
  • Analysis of Aurora A protein and enzymatic activity.
  • Assessment of AurA-TPX2 complex formation.
  • Investigation of TPX2 protein levels and mRNA translation.
  • Evaluation of APC/CDH1 involvement in TPX2 degradation.

Main Results:

  • Ionizing radiation (IR) impairs AurA interaction with TPX2 during mitosis.
  • IR leads to dephosphorylation of AurA at T288, inactivating the kinase.
  • Reduced TPX2 cellular levels contribute to decreased AurA-TPX2 complex formation.
  • TPX2 levels are decreased due to increased APC/CDH1-dependent degradation and reduced mRNA translation.

Conclusions:

  • DNA damage-induced G2 arrest involves the inactivation of Aurora A kinase.
  • The mechanism involves impaired AurA-TPX2 interaction, mediated by decreased TPX2 levels.
  • Both protein degradation and translational control regulate TPX2 levels post-irradiation.