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KMID : 0620920210530101602
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Experimental & Molecular Medicine
2021 Volume.53 No. 10 p.1602 ~ p.1611
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Thrap3 promotes R-loop resolution via interaction with methylated DDX5
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Kang Hyun-Je
Eom Hye-Jin
Kim Hong-Tae
Myung Kyung-Jae
Kwon Hyug-Moo
Choi Jang-Hyun
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Abstract
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Transcription-replication conflicts lead to DNA damage and genomic instability, which are closely related to human diseases. A major source of these conflicts is the formation of R-loops, which consist of an RNA-DNA hybrid and a displaced single-stranded DNA. Although these structures have been studied, many aspects of R-loop biology and R-loop-mediated genome instability remain unclear. Here, we demonstrate that thyroid hormone receptor-associated protein 3 (Thrap3) plays a critical role in regulating R-loop resolution. In cancer cells, Thrap3 interacts with DEAD-box helicase 5 (DDX5) and localizes to R-loops. Arginine-mediated methylation of DDX5 is required for its interaction with Thrap3, and the Thrap3-DDX5 axis induces the recruitment of 5’-3’ exoribonuclease 2 (XRN2) into R-loops. Loss of Thrap3 increases R-loop accumulation and DNA damage. These findings suggest that Thrap3 mediates resistance to cell death by preventing R-loop accumulation in cancer cells.
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KEYWORD
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Cancer genomics, DNA damage and repair
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