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Updated: Jul 10, 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

Effect of DNA damage on a BRCA1 complex

F Wu-Baer1, R Baer

  • 1Institute of Cancer Genetics and Department of Pathology, Columbia University College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, New York 10032, USA.

Nature
|November 2, 2001
PubMed

Insights

The BRCA1-CtIP complex remains stable after DNA damage, contrary to previous findings. Phosphorylation of CtIP by ATM kinase does not disrupt this interaction, impacting DNA damage response gene transcription.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The tumor suppressor BRCA1 protein interacts with CtIP, a substrate of ATM kinase.
  • Previous studies suggested that genotoxic stress disrupts the BRCA1-CtIP interaction via CtIP phosphorylation.

Purpose of the Study:

  • To investigate the effect of ionizing radiation and ATM kinase-mediated phosphorylation on the BRCA1-CtIP complex stability.
  • To determine if BRCA1-CtIP complex disruption mediates the transcription of DNA-damage-response genes.

Main Methods:

  • Investigated the stability of the BRCA1-CtIP complex in irradiated cells.
  • Analyzed the interaction of phosphorylated CtIP isoforms with BRCA1 in vivo.
  • Mapped the BRCA1-binding domain of CtIP relative to ATM phosphorylation sites.

Main Results:

  • The BRCA1-CtIP complex remains stable in cells exposed to ionizing radiation.
  • Phosphorylation of CtIP by ATM kinase does not prevent its in vivo interaction with BRCA1.
  • The BRCA1-binding domain of CtIP is distinct from ATM phosphorylation sites.

Conclusions:

  • Disruption of the BRCA1-CtIP complex is not the mechanism by which DNA-damage-response genes are induced after genotoxic stress.
  • The findings challenge the model proposed by Li et al. regarding BRCA1-CtIP complex dissociation and gene regulation.

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