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Myung, Kyung Jae
유전체 항상성 연구단
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Thrap3 promotes R-loop resolution via interaction with methylated DDX5

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Title
Thrap3 promotes R-loop resolution via interaction with methylated DDX5
Author(s)
Kang, Hyun Je; Eom, Hye-jin; Kim, Hongtae; Kyungjae Myung; Kwon, Hyug Moo; Choi, Jang Hyun
Publication Date
2021-10-01
Journal
Experimental and Molecular Medicine, v.53, no.10, pp.1602 - 1611
Publisher
Springer Nature
Abstract
© 2021, The Author(s).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.
URI
https://pr.ibs.re.kr/handle/8788114/10680
DOI
10.1038/s12276-021-00689-6
ISSN
1226-3613
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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