Related Experiment Video

Updated: Jun 19, 2026

Pooled CRISPR-Based Genetic Screens in Mammalian Cells
09:05

Pooled CRISPR-Based Genetic Screens in Mammalian Cells

Published on: September 4, 2019

Functional genomic screens identify CINP as a genome maintenance protein

Courtney A Lovejoy1, Xin Xu, Carol E Bansbach

  • 1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 6, 2009
PubMed

Insights

Researchers identified genes that trigger the DNA damage response (DDR) when deregulated. This discovery sheds light on maintaining genome integrity and preventing cancer by understanding cell-cycle control.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The DNA damage response (DDR) is crucial for maintaining genome integrity and preventing cancer.
  • DDR activation occurs due to DNA damage or aberrant cell division cycles.
  • Understanding genes that regulate DDR is vital for cancer research.

Purpose of the Study:

  • To identify genes that, when deregulated, activate the DDR in human cells.
  • To investigate the role of specific genes in genome stability and cancer predisposition.

Main Methods:

  • Utilized RNA interference (RNAi) and cDNA overexpression screens in human cells.
  • Conducted secondary RNAi screens to identify specific cell-cycle checkpoint proteins.

Main Results:

  • RNAi screen identified 73 genes causing DDR activation upon silencing, with some leading to increased micronuclei frequency.
  • cDNA screen identified 97 genes inducing DDR activation when overexpressed, many linked to cancer.
  • CDK2-interacting protein (CINP) was identified as a key cell-cycle checkpoint protein regulating ATR signaling.

Conclusions:

  • Deregulated genes can activate the DDR, impacting genome stability.
  • CINP plays a significant role in ATR-dependent signaling, replication stress resistance, and G2 checkpoint integrity.
  • Findings contribute to understanding cancer development and identifying potential therapeutic targets.

More Related Videos

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells08:38

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells

Published on: March 3, 2015

Generation of Centromere-Associated Protein-E CENP-E-/- Knockout Cell Lines using the CRISPR/Cas9 System11:49

Generation of Centromere-Associated Protein-E CENP-E-/- Knockout Cell Lines using the CRISPR/Cas9 System

Published on: June 23, 2023

Related Concept Videos

Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
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...
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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...