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Updated: Aug 6, 2026
06:44
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
HELZ-BRCA2 complex resolves R-loops to drive transcription-coupled homologous recombination
Wenjing Li1, Bo Wu1, Boya Gao2
1Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Nature Communications
|July 23, 2026
Summary
HELZ resolves R-loops, structures that harm genome stability, by interacting with BRCA2. This interaction is crucial for DNA repair and cancer cell survival, especially in high-transcription cancers.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- R-loops are nucleic acid structures formed during transcription that can impair genome stability and DNA repair if unresolved.
- BRCA2, a tumor suppressor, is known to regulate R-loops, but the mechanisms are unclear.
Purpose of the Study:
- To investigate the role of HELZ in R-loop regulation and its connection to BRCA2.
- To understand how HELZ-mediated R-loop resolution impacts DNA repair and cancer progression.
Main Methods:
- Identified HELZ as a direct interactor of BRCA2.
- Characterized HELZ as an ssRNA-specific R-loop resolvase.
- Assessed HELZ's role in DNA double-strand break repair and homologous recombination (HR).
Main Results:
- BRCA2 enhances HELZ's helicase activity and recruitment to R-loops.
- HELZ resolves R-loops at DNA double-strand breaks, promoting DNA end resection and HR in transcriptionally active regions.
- HELZ is essential for R-loop clearance in cancers like estrogen receptor-positive breast cancer, crucial for survival under transcriptional stress.
Conclusions:
- HELZ acts as a BRCA2-dependent regulator of R-loop homeostasis.
- HELZ facilitates homologous recombination repair by resolving R-loops at DNA breaks.
- HELZ is a potential biomarker and therapeutic target in R-loop-associated malignancies.
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