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Updated: Oct 7, 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

BRCA1 is a selective co-activator of 14-3-3 sigma gene transcription in mouse embryonic stem cells

O Aprelikova1, A J Pace, B Fang

  • 1Section of Molecular Signaling and Oncogenesis, Division of Clinical Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. apreliko@mail.nih.gov

The Journal of Biological Chemistry
|June 1, 2001
PubMed

Insights

BRCA1 deficiency impairs gene expression, particularly affecting stress response and cell cycle control. Loss of BRCA1 impacts the 14-3-3 sigma gene, crucial for G2/M checkpoint arrest after radiation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • BRCA1 is a tumor suppressor gene critical for breast and ovarian cancer prevention.
  • Its roles in DNA repair and transcription are well-established.
  • Understanding BRCA1's function in transcriptional regulation is key to cancer biology.

Purpose of the Study:

  • To investigate the role of BRCA1 in transcriptional regulation.
  • To analyze gene expression profiles in BRCA1-deficient mouse embryonic stem cells.

Main Methods:

  • Microarray technology was employed to analyze gene expression profiles.
  • Comparison of gene expression between BRCA1-deficient and wild-type cells.

Main Results:

  • Loss of BRCA1 led to decreased expression of stress response, cytoskeleton, and protein metabolism genes.
  • BRCA1 deficiency specifically down-regulated the p53 target gene 14-3-3 sigma.
  • BRCA1-deficient cells failed to maintain G2/M growth arrest post-ionizing radiation exposure.

Conclusions:

  • BRCA1 is essential for the proper transcriptional regulation of key cellular processes.
  • BRCA1's induction of 14-3-3 sigma is p53-dependent and involves a p53 response element.
  • BRCA1 deficiency compromises the G2/M checkpoint, impacting cellular response to DNA damage.

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