Related Experiment Video

Updated: Jul 1, 2026

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
08:31

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

Published on: June 8, 2018

BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure

Haijuan Yang1, Philip D Jeffrey, Julie Miller

  • 1Department of Pharmacology, Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.

Science (New York, N.Y.)
|September 14, 2002
PubMed

Insights

BRCA2 mutations cause cancer by disrupting DNA repair. This study reveals the BRCA2 structure, showing how it binds DNA and aids homologous recombination, crucial for fixing double-strand breaks.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Mutations in BRCA2 (breast cancer susceptibility gene 2) are linked to chromosomal instability.
  • Defects in homologous recombination repair of double-strand DNA breaks (DSBs) are implicated, but BRCA2's precise role remains unclear.

Purpose of the Study:

  • To elucidate the structural and biochemical mechanisms of BRCA2 in homologous recombination.
  • To provide a molecular basis for BRCA2-associated cancers.

Main Methods:

  • X-ray crystallography to determine the structure of a BRCA2 domain bound to DSS1 and DNA.
  • Biochemical assays to assess DNA binding and recombination activity.

Main Results:

  • The crystal structure of a ~90 kDa BRCA2 domain reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif.
  • Demonstrated BRCA2 domain binds single-stranded DNA and implicated the HTH motif in double-stranded DNA binding.
  • Showed BRCA2 directly stimulates RAD51-mediated recombination in vitro.

Conclusions:

  • BRCA2 plays a direct role in homologous recombination, essential for repairing DSBs.
  • Structural and biochemical data provide a foundation for understanding BRCA2-related cancers and DNA repair defects.

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Related Concept Videos

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...
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...
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...
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...
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...
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...