Nature communications · 2026
HELZ is a RNA-DNA helicase that resolves R loops to facilitate homologous recombination repair.
СтатьяResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод пока не подготовлен
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Haji-Seyed-Javadi Ramona, Koyen Allyson E, Rath Sandip K, Wu Bo, Madden Matthew Z, Hou Yingzi, Kapoor-Vazirani Priya, Roshika Roshika, Aiello Meili, Luong Nho Cong, Tseng Wei-Che, Sesay Fatmata, Kim John S, Tan Tony, Kim Seohyun, Gao Boya, Song Boying S, Kenney Anna M, Connolly Erin C, Yang Lily, Xhemalce Blerta, Li Xiaoxian, Switchenko Jeffrey M, Yang Xiaofeng, Buchwald Zachary S, Deng Xingming, Miller Kyle M, Yao Bing, Lan Li, Zhao Weixing, Yu David S
Аннотация
R loop homeostasis is critical for DNA double-strand break (DSB) repair; however, how R loops are resolved in this context is poorly understood. Here, we define HELZ as a unique RNA-DNA helicase that resolves R loops to facilitate homologous recombination (HR) repair. From a synthetic lethal etoposide resistance siRNA screen, we found that HELZ depletion causes R loop-mediated hypersensitivity to DSB-inducing agents, and HELZ localizes and binds to DSBs. HELZ preferentially binds to and unwinds RNA-DNA hybrids with 5'ssRNA overhangs to promote R loop resolution genome-wide and at DSBs. Interestingly, HELZ facilitates BRCA1 recruitment to DSBs by preventing R loop accumulation, thereby promoting DNA end resection and HR to prevent R loop mediated genomic instability. In summary, we show that HELZ resolves R loops critical for HR, thereby promoting genome stability and resistance to DSB-inducing agents.