DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability
Journal
Nature communications
Journal Volume
15
Journal Issue
1
Start Page
6009
ISSN
2041-1723
Date Issued
2024-12
Author(s)
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
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.
SDGs
Type
journal article