Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Restarting Stalled Replication Forks

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,...

Conservative Site-specific Recombination and Phase Variation

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...

Histone Variants at the Centromere

Histone Variants at the Centromere

Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...

You might also read

Related Articles

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

Sort by

Same author

Genetic drivers of etiologic heterogeneity in thyroid cancer.

Nature communications·2026

Same author

Cumulative breastfeeding duration and incidence of diabetes in the multiethnic cohort study.

Global perspectives on nutrition·2026

Same author

The survival double descent: generalization dynamics of deep neural networks in time-to-event analysis.

BMC medical research methodology·2026

Same author

Multi-ancestry transcriptome-wide association studies uncover insights into breast cancer genetics and biology.

Nature communications·2026

Same author

Polygenic risk score with KLK3 SNP-SNP interaction pairs for predicting prostate cancer aggressiveness.

Communications medicine·2026

Same author

Generalizability of an AI-based mammogram risk score (MRS) for breast cancer among diverse populations of women.

Science advances·2026

Search research articles

Related Experiment Video

Updated: Jul 28, 2025

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating

Chunling Hu¹, Anil Belur Nagaraj¹, Hermela Shimelis¹

¹Mayo Clinic, Rochester, Minnesota.

Cancer Research

|May 30, 2023

Summary

Functional analysis of RAD51C missense variants reveals 30 deleterious variants impacting DNA repair and increasing breast and ovarian cancer risk, aiding clinical classification.

More Related Videos

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

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

Published on: February 13, 2019

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Published on: August 21, 2016

Related Experiment Videos

Last Updated: Jul 28, 2025

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

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

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

Published on: February 13, 2019

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA

Published on: August 21, 2016

Area of Science:

Genetics
Molecular Biology
Cancer Research

Background:

Pathogenic protein-truncating variants in RAD51C, a key DNA damage repair gene, are linked to increased breast and ovarian cancer risk.
Numerous RAD51C missense variants of uncertain significance (VUS) exist, with their functional impact and cancer predisposition largely uncharacterized.

Purpose of the Study:

To functionally assess a large cohort of RAD51C missense variants.
To determine the impact of these variants on RAD51C function and their association with cancer risk.

Main Methods:

A homology-directed repair (HDR) assay was employed in reconstituted RAD51C-/- cells to evaluate 173 missense variants.
Functional assays in reconstituted RAD51C-depleted cancer cells and computational structural analysis were also performed.
Case-control association studies were conducted to assess cancer risk in carriers of deleterious variants.

Main Results:

Thirty deleterious RAD51C missense variants were identified, with 18 located in a critical ATP-binding region.
Deleterious variants impaired RAD51C function, conferred sensitivity to cisplatin and olaparib, and disrupted protein complex formation.
These variants showed significant associations with moderate breast cancer risk (OR, 3.92) and high ovarian cancer risk (OR, 14.8).

Conclusions:

Functional characterization of RAD51C missense variants provides crucial insights into their role in DNA repair and cancer predisposition.
The identified deleterious variants are functionally similar to known pathogenic protein-truncating variants.
This data supports classifying inactivating RAD51C missense variants as pathogenic or likely pathogenic, potentially improving clinical management for carriers.