Related Experiment Video

Updated: Apr 1, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

14.7K

The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1

Erik Voets1, Judith Marsman1, Jeroen Demmers2

  • 1Division of Cell Biology I (B5) and Division of Molecular Carcinogenesis (B7), The Netherlands Cancer Insitute (NKI-AvL), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Scientific Reports
|October 2, 2015
PubMed

Insights

Cyclin-dependent kinase 1 (Cdk1) inhibition causes cell death by creating chromosome alignment errors. This is prevented by suppressing PRC1-1 and KIF4, crucial for proper mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cyclin-dependent kinase 1 (Cdk1) is vital for cell division, and its inhibition leads to mitotic defects and aneuploidy.
  • Understanding the genetic factors influencing Cdk1 inhibitor toxicity is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify human genes that determine cellular toxicity upon Cdk1 inhibition using a large-scale RNAi screen.
  • To elucidate the molecular mechanisms underlying Cdk1 inhibition-induced cell death.

Main Methods:

  • Large-scale RNA interference (RNAi) screen in human cells.
  • Analysis of mitotic progression, chromosome alignment, and spindle checkpoint activity.
  • Investigating the roles of PRC1-1 and KIF4 in Cdk1 inhibition toxicity.

Main Results:

  • Cdk1 inhibition causes sister chromatid alignment errors and mitotic arrest.
  • Depletion of PRC1-1 or KIF4, or abrogating KIF4 motor activity, alleviates Cdk1 inhibition toxicity.
  • Cdk1 activity normally prevents KIF4-dependent PRC1-1 translocation, ensuring proper chromosome congression.

Conclusions:

  • Cell death from Cdk1 inhibitors is directly linked to chromosome alignment defects.
  • These defects arise from insufficient repression of PRC1-1 and KIF4 during prometaphase.
  • Maintaining adequate Cdk1 activity is essential for repressing KIF4-PRC1-1 interactions and safeguarding mitosis.

More Related Videos

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

15.1K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

11.4K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
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...
10.4K
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...
3.4K
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...
4.7K
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,...
6.6K