Related Experiment Video

Updated: Jun 5, 2026

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
06:25

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

Tumour suppressor ING1b maintains genomic stability upon replication stress

Ronald P C Wong1, Hanyang Lin, Shahram Khosravi

  • 1Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, ON, Canada V6H 3Z6.

Nucleic Acids Research
|January 14, 2011
PubMed

Insights

Tumor suppressor ING1b preserves genomic stability by regulating proliferating cell nuclear antigen (PCNA) monoubiquitination. ING1b deficiency impairs DNA lesion bypass, increasing cancer risk.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The lesion bypass pathway, regulated by proliferating cell nuclear antigen (PCNA) monoubiquitination, is crucial for resolving DNA replication stalling.
  • Genomic instability and cancer development are linked to defects in DNA repair pathways.
  • Tumor suppressor p33ING1 (ING1b) deficiency causes hypersensitivity to DNA damaging agents through an uncharacterized mechanism.

Purpose of the Study:

  • To elucidate the novel tumor suppressive function of ING1b in maintaining genomic stability during replication stress.
  • To investigate the role of ING1b in regulating PCNA monoubiquitination and its impact on DNA lesion bypass.

Main Methods:

  • Knockdown of ING1b in cells.
  • Assessment of sensitivity to UV irradiation and DNA damaging agents.
  • Analysis of PCNA monoubiquitination status.
  • Investigation of ING1b's interaction with Rad18 and its role in lesion bypass.
  • Evaluation of histone H4 acetylation and chromatin remodeling.

Main Results:

  • ING1b knockdown cells exhibit increased sensitivity to UV due to impaired recovery from replication blockage, leading to genomic instability.
  • ING1b is essential for Rad18-mediated PCNA monoubiquitination during lesion bypass.
  • ING1b-dependent PCNA monoubiquitination is linked to histone H4 acetylation.
  • Chromatin remodeling contributes to stalled replication fork stabilization and PCNA monoubiquitination regulation.

Conclusions:

  • ING1b plays a critical role in preserving genomic stability by regulating PCNA monoubiquitination during replication stress.
  • ING1b's function in lesion bypass is mediated through its regulation of PCNA monoubiquitination and associated chromatin modifications.
  • These findings reveal a novel tumor suppressive mechanism involving ING1b, PCNA, and chromatin remodeling, offering potential therapeutic targets for cancer prevention.

More Related Videos

Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay05:55

Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay

Published on: August 23, 2024

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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.
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...