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The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export.
Olazabal-Herrero, Anne; He, Boxue; Kwon, Youngho; Gupta, Abhishek K; Dutta, Arijit; Huang, Yuxin; Boddu, Prajwal; Liang, Zhuobin; Liang, Fengshan; Teng, Yaqun; Lan, Li; Chen, Xiaoyong; Pei, Huadong; Pillai, Manoj M; Sung, Patrick; Kupfer, Gary M.
Afiliación
  • Olazabal-Herrero A; Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
  • He B; Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 41001
  • Kwon Y; Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Gupta AK; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
  • Dutta A; Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Huang Y; Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Boddu P; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
  • Liang Z; Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
  • Liang F; Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
  • Teng Y; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
  • Lan L; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
  • Chen X; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA.
  • Pei H; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
  • Pillai MM; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
  • Sung P; Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: sungp@uthscsa.edu.
  • Kupfer GM; Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA. Electronic address: gary.kupfer@georgetown.edu.
Cell Rep ; 43(1): 113610, 2024 01 23.
Article en En | MEDLINE | ID: mdl-38165804
ABSTRACT
Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, and cancer susceptibility. The central FA protein complex FANCI/FANCD2 (ID2) is activated by monoubiquitination and recruits DNA repair proteins for interstrand crosslink (ICL) repair and replication fork protection. Defects in the FA pathway lead to R-loop accumulation, which contributes to genomic instability. Here, we report that the splicing factor SRSF1 and FANCD2 interact physically and act together to suppress R-loop formation via mRNA export regulation. We show that SRSF1 stimulates FANCD2 monoubiquitination in an RNA-dependent fashion. In turn, FANCD2 monoubiquitination proves crucial for the assembly of the SRSF1-NXF1 nuclear export complex and mRNA export. Importantly, several SRSF1 cancer-associated mutants fail to interact with FANCD2, leading to inefficient FANCD2 monoubiquitination, decreased mRNA export, and R-loop accumulation. We propose a model wherein SRSF1 and FANCD2 interaction links DNA damage response to the avoidance of pathogenic R-loops via regulation of mRNA export.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anemia de Fanconi / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anemia de Fanconi / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos