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DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.
Yang, Bing-Ze; Liu, Mei-Yin; Chiu, Kuan-Lin; Chien, Yuh-Ling; Cheng, Ching-An; Chen, Yu-Lin; Tsui, Li-Yu; Lin, Keng-Ru; Chu, Hsueh-Ping Catherine; Wu, Ching-Shyi Peter.
Afiliación
  • Yang BZ; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Liu MY; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Chiu KL; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106319, Taiwan.
  • Chien YL; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Cheng CA; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Chen YL; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Tsui LY; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Lin KR; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan.
  • Chu HC; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106319, Taiwan.
  • Wu CP; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 100233, Taiwan. cswu2017@ntu.edu.tw.
Nat Commun ; 15(1): 6009, 2024 Jul 17.
Article en En | MEDLINE | ID: mdl-39019926
ABSTRACT
RNA helicase DHX9 is essential for genome stability by resolving aberrant R-loops. However, its regulatory mechanisms remain unclear. Here we show that SUMOylation at lysine 120 (K120) is crucial for DHX9 function. Preventing SUMOylation at K120 leads to R-loop dysregulation, increased DNA damage, and cell death. Cells expressing DHX9 K120R mutant which cannot be SUMOylated are more sensitive to genotoxic agents and this sensitivity is mitigated by RNase H overexpression. Unlike the mutant, wild-type DHX9 interacts with R-loop-associated proteins such as PARP1 and DDX21 via SUMO-interacting motifs. Fusion of SUMO2 to the DHX9 K120R mutant enhances its association with these proteins, reduces R-loop accumulation, and alleviates survival defects of DHX9 K120R. Our findings highlight the critical role of DHX9 SUMOylation in maintaining genome stability by regulating protein interactions necessary for R-loop balance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inestabilidad Genómica / ARN Helicasas DEAD-box / Sumoilación / Estructuras R-Loop Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inestabilidad Genómica / ARN Helicasas DEAD-box / Sumoilación / Estructuras R-Loop Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido