DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
received:
04
09
2023
accepted:
09
07
2024
medline:
18
7
2024
pubmed:
18
7
2024
entrez:
17
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39019926
doi: 10.1038/s41467-024-50428-4
pii: 10.1038/s41467-024-50428-4
doi:
Substances chimiques
DEAD-box RNA Helicases
EC 3.6.4.13
DHX9 protein, human
EC 3.6.1.-
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
DDX21 protein, human
EC 3.6.1.-
PARP1 protein, human
EC 2.4.2.30
Lysine
K3Z4F929H6
SUMO2 protein, human
0
Small Ubiquitin-Related Modifier Proteins
0
Neoplasm Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6009Subventions
Organisme : National Taiwan University (NTU)
ID : CDP-111L7737, 112L7720, and 113L7704
Informations de copyright
© 2024. The Author(s).
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