Related Experiment Video

Updated: Jan 18, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

11.0K

RAD51 is chromatin enriched and targetable in BRCA1-deficient cells

Min Peng1, Silviana Lee1, Hitha Gopalan Nair1

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Molecular Cell
|September 11, 2025
PubMed

Insights

BRCA1 mutant cancers exhibit RAD51 enrichment on chromatin, crucial for cell survival due to ssDNA gaps. Targeting this RAD51 engagement offers a new strategy for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • BRCA1 mutant cancers are homologous recombination (HR) deficient.
  • This deficiency is linked to sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi).
  • RAD51 foci are established biomarkers for PARPi response, but single-stranded DNA (ssDNA) gaps also play a role.

Purpose of the Study:

  • To investigate the role of RAD51 in BRCA1-deficient cells.
  • To explore the relationship between RAD51 chromatin enrichment, ssDNA gaps, and PARPi sensitivity.
  • To understand the mechanisms underlying PARPi resistance.

Main Methods:

  • Analysis of RAD51 foci and chromatin enrichment in BRCA1-deficient cells.
  • Genetic manipulation involving deletion of 53BP1, MDC1, and H2AX.
  • Assessment of poly (ADP-ribose) polymerase inhibitor (PARPi) resistance.

Main Results:

  • RAD51 is essential and enriched in the chromatin of BRCA1-deficient cells.
  • Loss of 53BP1 alleviates RAD51 enrichment and dependency.
  • Loss of MDC1 or H2AX leads to PARPi resistance but does not restore RAD51 foci, uncoupling HR from resistance.

Conclusions:

  • ssDNA gaps in BRCA1-deficient cells drive post-replicative RAD51 chromatin engagement for cell fitness.
  • This RAD51 engagement represents a targetable vulnerability in BRCA1 mutant cancers.
  • The findings challenge the direct correlation between RAD51 foci and PARPi response in certain contexts.
Keywords:
53BP1BRCA1H2AXHRMDC1PARPiRAD51TLSfocigaps

More Related Videos

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

5.9K
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA108:53

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

Published on: February 17, 2011

15.0K

Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.3K
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...
10.0K
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...
3.0K
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
62.7K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.7K