Related Experiment Video

Updated: Mar 16, 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

A role for the spindle assembly checkpoint in the DNA damage response

Roger Palou1, Gloria Palou1, David G Quintana2

  • 1Biophysics Unit, School of Medicine, and Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Bellaterra, 08193, Catalonia, Spain.

Current Genetics
|August 5, 2016
PubMed

Insights

The spindle assembly checkpoint (SAC) helps stabilize Pds1/securin, preventing chromosome segregation during DNA damage or replication stress, even when the S phase checkpoint is absent. This reveals a crucial role for the SAC in the DNA Damage Response (DDR).

Area of Science:

  • Cellular biology
  • Genomics
  • Cancer research

Background:

  • Spontaneous DNA damage threatens genomic integrity, leading to genomic instability and cancer.
  • The DNA Damage Response (DDR) is a critical anti-cancer barrier in human cells.
  • The DDR prevents aneuploidy by blocking segregation of damaged or incompletely replicated chromosomes.

Purpose of the Study:

  • To investigate the mechanisms controlling anaphase blockage during replication stress.
  • To determine the role of Pds1/securin stabilization in response to genotoxic stress.
  • To elucidate the interplay between the S phase checkpoint and the spindle assembly checkpoint (SAC) in maintaining genomic integrity.

Main Methods:

  • Utilized mec1/ATR tel1/ATM double null mutants to abrogate the S phase checkpoint.
  • Exposed cells to genotoxic stress to observe Pds1/securin stabilization.
  • Disrupted both the SAC and S phase checkpoint to assess their combined effect on chromosome segregation.

Main Results:

  • Pds1/securin stabilization occurs in a SAC-dependent manner even when the S phase checkpoint is completely abrogated.
  • Disrupting both the SAC and S phase checkpoint allows chromosome segregation despite DNA damage or replication stress.
  • The SAC acts as an independent control layer within the DDR.

Conclusions:

  • The spindle assembly checkpoint (SAC) is an integral part of the DNA Damage Response (DDR).
  • The DDR employs multiple, independent control layers to maintain genomic integrity during replication challenges.
  • Understanding these checkpoints is crucial for developing cancer therapies targeting genomic instability.
Keywords:
Chromosome segregationCyclin Dependent Kinase (Cdk1)DNA damage response (DDR)Genomic instabilityS Phase checkpointSpindle assembly checkpoint (SAC)

More Related Videos

Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos07:46

Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos

Published on: June 23, 2023

3.4K
Study of the DNA Damage Checkpoint using Xenopus Egg Extracts10:55

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts

Published on: November 5, 2012

17.2K

Related Concept Videos

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...
3.9K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

1.8K
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...
10.3K
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...
3.3K
Spindle Assembly02:50

Spindle Assembly

Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
4.4K
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,...
6.5K