Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

5.9K
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,...
5.9K
Homologous Recombination02:31

Homologous Recombination

52.8K
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...
52.8K
The DNA Replication Fork01:02

The DNA Replication Fork

37.0K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
37.0K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.3K
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...
9.3K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

12.9K
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...
12.9K
The Replisome03:01

The Replisome

35.1K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
35.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

An Analytic Framework Characterizes the Biological Processes That Shape Copy Number-Based Genome Instability Patterns in Breast Cancer.

Cancer research·2026
Same author

Proteostasis Deregulation by Metabolism Drives the Hallmarks of Cancer.

Annual review of biochemistry·2026
Same author

EEPD1 evolved a unique DNA clamping dimer protecting reversed replication forks.

Nucleic acids research·2026
Same author

HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks.

iScience·2026
Same author

Editorial: Overcoming resistance in DDR inhibition: new targets and therapeutic strategies.

Frontiers in molecular biosciences·2026
Same author

Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.

The Journal of clinical investigation·2026

Related Experiment Video

Updated: Sep 20, 2025

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication
05:55

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication

Published on: August 23, 2024

661

BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability.

Michael A Longo1, Syed Moiz Ahmed2, Yue Chen3

  • 1Department of Molecular & Cellular Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.

Molecular Cell
|May 29, 2025
PubMed
Summary
This summary is machine-generated.

Breast cancer susceptibility protein 2 (BRCA2) and RAD51 interaction was re-evaluated. New findings reveal BRCA2 C terminus switches RAD51 function from DNA repair to fork protection, impacting cancer etiology.

Keywords:
BRCA2Rad51SIRFcancercrystal structuregenome stabilityhomology-directed repairreplication fork protection

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.4K
Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
06:24

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

Published on: February 13, 2019

8.1K

Related Experiment Videos

Last Updated: Sep 20, 2025

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication
05:55

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication

Published on: August 23, 2024

661
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.4K
Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
06:24

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

Published on: February 13, 2019

8.1K

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Cancer Research

Background:

  • Breast cancer susceptibility protein 2 (BRCA2) and RAD51 are crucial for DNA repair and genome stability.
  • The BRCA2 C terminus was believed to stabilize RAD51 for homology-directed DNA-break repair (HDR).

Purpose of the Study:

  • To elucidate the structural mechanism of BRCA2-RAD51 interaction in DNA repair and replication fork protection (FP).
  • To challenge the established model of BRCA2-RAD51 function in cancer etiology and therapy resistance.

Main Methods:

  • Detailed crystal structure determination of the BRCA2 C-terminal interaction domain (TR2i) complexed with ATP-bound RAD51.
  • Biochemical assays and molecular analyses using interface-guided mutations.

Main Results:

  • The BRCA2 TR2i domain induces a unique ATP-RAD51 dimer conformation, promoting double-stranded B-DNA binding.
  • This interaction facilitates replication fork protection (FP) over homology-directed repair (HDR) by allosterically regulating RAD51.
  • A cyclin-dependent kinase (CDK) phosphorylation site on BRCA2 (S3291/P3292) modulates RAD51 activity between FP and HDR phases.

Conclusions:

  • The BRCA2 C terminus acts as an allosteric clamp, switching RAD51's DNA binding preference from single-stranded to double-stranded DNA.
  • This mechanism enforces replication fork protection (FP) during S phase, challenging the prevailing BRCA2-RAD51 dogma.
  • Understanding this switch is critical for cancer etiology and developing novel therapeutic strategies against therapy-resistant cancers.