دورية أكاديمية
أعرض في EDS

DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.

التفاصيل البيبلوغرافية
العنوان: DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.
المؤلفون: 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.
المصدر: Nature communications [Nat Commun] 2024 Jul 17; Vol. 15 (1), pp. 6009. Date of Electronic Publication: 2024 Jul 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Sumoylation* , DEAD-box RNA Helicases*/metabolism , DEAD-box RNA Helicases*/genetics , Genomic Instability* , R-Loop Structures*, Humans ; HEK293 Cells ; DNA Damage ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Poly (ADP-Ribose) Polymerase-1/genetics ; Lysine/metabolism ; Mutation ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Small Ubiquitin-Related Modifier Proteins/genetics ; Neoplasm Proteins
مستخلص: 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.
(© 2024. The Author(s).)
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معلومات مُعتمدة: CDP-111L7737, 112L7720, and 113L7704 National Taiwan University (NTU)
المشرفين على المادة: EC 3.6.4.13 (DEAD-box RNA Helicases)
EC 3.6.1.- (DHX9 protein, human)
EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
EC 3.6.1.- (DDX21 protein, human)
EC 2.4.2.30 (PARP1 protein, human)
K3Z4F929H6 (Lysine)
0 (SUMO2 protein, human)
0 (Small Ubiquitin-Related Modifier Proteins)
0 (Neoplasm Proteins)
تواريخ الأحداث: Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240816
رمز التحديث: 20240816
مُعرف محوري في PubMed: PMC11255299
DOI: 10.1038/s41467-024-50428-4
PMID: 39019926
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-50428-4