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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...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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...
Attachment of Sister Chromatids02:57

Attachment of Sister Chromatids

As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules.  Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

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Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
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ATM-mediated NuSAP phosphorylation induces mitotic arrest.

Ping Xie1, Lu Li, Guichun Xing

  • 1School of Life Sciences, Tsinghua University, Beijing 100084, China.

Biochemical and Biophysical Research Communications
|December 7, 2010
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Summary

NuSAP, a microtubule protein, triggers mitotic arrest via ATM kinase activity. This ATM-dependent pathway targets NuSAP to prevent cell division, revealing a novel cell cycle checkpoint.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • NuSAP is a crucial microtubule-associated protein essential for spindle assembly, with deficiency causing embryonic lethality.
  • ATM kinase regulates G1/S control, but its role in G2/M phase progression remains unclear.

Purpose of the Study:

  • To investigate the role of ATM kinase in regulating mitotic progression in response to NuSAP expression.
  • To elucidate the molecular mechanism linking NuSAP and ATM during the cell cycle.

Main Methods:

  • Ectopic expression of NuSAP in cells.
  • Depletion of endogenous ATM or inhibition of its kinase activity.
  • Co-immunoprecipitation assays to detect protein interactions.
  • Western blotting to assess protein phosphorylation.

Main Results:

  • Ectopic NuSAP expression induced mitotic arrest dependent on ATM kinase activity.
  • NuSAP failed to cause mitotic arrest when ATM was depleted or inhibited.
  • ATM directly interacts with NuSAP and phosphorylates it at Ser124 during G2/M phase.

Conclusions:

  • A novel ATM-dependent checkpoint pathway involving NuSAP has been identified.
  • This pathway prevents premature mitotic progression by targeting the microtubule-associated protein NuSAP.
  • ATM's role extends to regulating G2/M phase through interaction with NuSAP.