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

Autor: Bing-Ze Yang, Mei-Yin Liu, Kuan-Lin Chiu, Yuh-Ling Chien, Ching-An Cheng, Yu-Lin Chen, Li-Yu Tsui, Keng-Ru Lin, Hsueh-Ping Catherine Chu, Ching-Shyi Peter Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-50428-4
Popis: 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.
Databáze: Directory of Open Access Journals