Related Experiment Video

Updated: May 9, 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

BRCA2 affects the efficiency of DNA double-strand break repair in response to N-nitroso compounds with differing

Wen-Ting Zhao1, Yu-Tian Wang, Zhao-Wei Huang

  • 1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai 200031;

Oncology Letters
|July 9, 2013
PubMed

Insights

N-nitroso compounds (NOCs) induce DNA damage, but their repair varies. BRCA2 plays a role in repairing DNA double-strand breaks (DSBs) caused by NOCs, influencing carcinogenic risk.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Toxicology

Background:

  • BRCA2 is crucial for DNA double-strand break (DSB) repair via homologous recombination (HR).
  • N-nitrosodiethylamine (NDEA), N-nitrosodiethanolamine (NDELA), and N-nitrosodipropylamine (NDPA) are N-nitroso compounds (NOCs) with varying carcinogenic risks despite similar structures.
  • The differential carcinogenic effects of NOCs may stem from distinct DNA damage response pathways.

Purpose of the Study:

  • To investigate the formation of DSBs induced by NDEA, NDELA, and NDPA.
  • To determine the involvement of BRCA2 in the cellular response to DNA damage caused by these NOCs.
  • To explore the relationship between BRCA2-mediated repair and the genotoxic-carcinogenic potential of NOCs.

Main Methods:

  • Induction of DSBs and γ-H2AX expression in SGC7901 gastric cancer cells by NOCs.
  • Assessment of DNA damage repair efficiency for NDEA, NDELA, and NDPA.
  • Analysis of BRCA2 and RAD51 expression following NOC treatment.
  • BRCA2 knockdown experiments to evaluate its role in DNA repair and cellular sensitivity to NOCs.

Main Results:

  • NOCs induced DSBs and γ-H2AX expression in a time-dependent manner.
  • NDEA, a potent carcinogen, induced DNA damage that was repaired less efficiently than that caused by NDELA or NDPA.
  • NDEA inhibited BRCA2 and RAD51 expression, while NDELA and NDPA upregulated them.
  • BRCA2 knockdown impaired DSB repair induced by NDELA/NDPA and increased sensitivity to these NOCs, but not NDEA.

Conclusions:

  • A BRCA2-mediated pathway contributes to differential DSB repair and sensitivity following NOC exposure.
  • BRCA2's role in DNA repair may be associated with the varying genotoxic-carcinogenic potential of different NOCs.
  • Understanding BRCA2's involvement offers insights into cancer risk associated with NOC exposure.
Keywords:
BRCA2DNA damage repairDNA double strand breaksN-nitroso compounds

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Base Excision Repair01:54

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...