Identification of BRCA2-DSS1 new partner HELZ

R-loops are dynamic three-stranded nucleic acid structures that regulate genome function but can threaten genome stability if not properly resolved. BRCA2, a key player in homologous recombination (HR), also regulates R-loops, though the mechanisms remain unclear. To uncover novel R-loop regulators, we employed a BioID-DSS1 proximity labeling system, leveraging DSS1’s stable interaction with BRCA2 to map its protein interaction network under DNA damage conditions. This approach identified HELZ, a putative RNA helicase, as a new BRCA2-DSS1 interactor. We found that HELZ functions as an RNA-specific R-loop resolvase, revealing a previously unrecognized BRCA2-HELZ axis in R-loop resolution. This work provides new insights into how BRCA2 safeguards genome integrity beyond its canonical role in HR.