Helicases

Helicases are ATP-driven nucleic acid motor enzymes that translocate along DNA or RNA, unwind duplex substrates, and disrupt protein-nucleic acid interactions^[1]. Mechanistically, helicases support DNA replication, repair, recombination, transcription, ribosome biogenesis, RNA splicing, RNA transport, RNA editing, and RNA degradation^[1][2]. In disease-relevant models, human RECQ helicases maintain genome stability, and loss of BLM, WRN, or RECQL4 function causes Bloom syndrome, Werner syndrome, and Rothmund-Thomson-related syndromes^[3]. Compared with RECQ DNA helicases, DDX3X is an X-linked DEAD-box RNA helicase with a Y-linked paralog, DDX3Y, and DDX3X-linked conditions can show sex differences related to paralog expression or function^[4]. For experimental applications, ML216 inhibits BLM DNA unwinding activity and modulates chromosome stability in human cells^[5]. DDX3X inhibitors have been designed, validated on the target enzyme, and evaluated against West Nile virus infection, supporting helicase inhibition as a tool for antiviral research^[6]. RK-33 has also been used to target DDX3X in breast cancer bone metastasis models^[7].