Related Experiment Video

Updated: Jun 16, 2026

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
08:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

Hemizygosity for Atm and Brca1 influence the balance between cell transformation and apoptosis

Fengtao Su1, Lubomir B Smilenov, Thomas Ludwig

  • 1Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.

Radiation Oncology (London, England)
|February 24, 2010
PubMed
Abstract

Insights

Monoallelic loss of ATM or BRCA1 genes increases radiation-induced cell transformation and reduces apoptosis. Combined loss exacerbates these effects, highlighting the ATM/BRCA1 network

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Loss of one gene copy (allelic loss) in DNA repair pathways is linked to genomic instability and cancer.
  • Studies in mouse models show that losing one copy of related genes can amplify tumor development.
  • Investigating the impact of monoallelic loss of ATM and BRCA1 on radiation-induced cell changes is crucial.

Purpose of the Study:

  • To determine the role of monoallelic loss of ATM and BRCA1 in radiation-induced cell transformation.
  • To assess the effect of monoallelic loss of ATM and BRCA1 on radiation-induced apoptosis.
  • To understand the combined effects of haploinsufficiency for ATM and BRCA1.

Main Methods:

  • Mouse embryo fibroblasts (MEF) were used to measure cell transformation.
  • Thymocytes were used to measure apoptosis.
  • Experiments involved comparing wild-type and hemizygous genotypes for ATM and BRCA1.

Main Results:

  • Haploinsufficiency for ATM or BRCA1 increased radiation-induced transformation in MEF.
  • Haploinsufficiency for ATM or BRCA1 decreased radiation-induced apoptosis in thymocytes.
  • Combined haploinsufficiency for both ATM and BRCA1 showed a more pronounced effect on apoptosis.

Conclusions:

  • The ATM/BRCA1 cell signaling network's DNA repair efficiency under stress is dependent on the expression levels of both ATM and BRCA1.
  • Monoallelic loss of ATM or BRCA1 impairs DNA repair capacity, leading to increased genomic instability.
  • These findings underscore the importance of both ATM and BRCA1 in maintaining genomic integrity and preventing cancer.

More Related Videos

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures08:41

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures

Published on: December 27, 2024

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

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 Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...