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RNA Helicase DDX3 Regulates RAD51 Localization and DNA Damage Repair in Ewing Sarcoma.
Randolph, Matthew E; Afifi, Marwa; Gorthi, Aparna; Weil, Rachel; Wilky, Breelyn A; Weinreb, Joshua; Ciero, Paul; Ter Hoeve, Natalie; van Diest, Paul J; Raman, Venu; Bishop, Alexander J R; Loeb, David M.
Afiliación
  • Randolph ME; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
  • Afifi M; Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY.
  • Gorthi A; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Weil R; Greehey Children's Cancer Research Institute and Department of Cell Systems & Anatomy, UT Health San Antonio, San Antonio, TX.
  • Wilky BA; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
  • Weinreb J; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
  • Ciero P; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
  • Ter Hoeve N; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
  • van Diest PJ; Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY.
  • Raman V; Department of Pathology, University Medical Centre Utrecht, The Netherlands.
  • Bishop AJR; Department of Pathology, University Medical Centre Utrecht, The Netherlands.
  • Loeb DM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
bioRxiv ; 2023 Jun 10.
Article en En | MEDLINE | ID: mdl-37333164
We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2. In particular, DDX3 colocalizes with RAD51 and RNA:DNA hybrid structures in the cytoplasm of EWS cells. Inhibition of DDX3 RNA helicase activity increases cytoplasmic RNA:DNA hybrids, sequestering RAD51 in the cytoplasm, which impairs nuclear translocation of RAD51 to sites of double-stranded DNA breaks thus increasing sensitivity of EWS to radiation treatment, both in vitro and in vivo. This discovery lays the foundation for exploring new therapeutic approaches directed at manipulating DDR protein localization in solid tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos