File Download

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
Related Researcher


Lee, Ja Yil
Biochemistry and Molecular Biophysics Lab.
Read More

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

Full metadata record

DC Field Value Language
dc.citation.title LEUKEMIA - Hwang, Won Chan - Park, Kibeom - Park, Silvia - Cheon, Na Young - Lee, Ja Yil - Hwang, Taejoo - Lee, Semin - Lee, Jong-Mi - Ju, Min Kyung - Lee, Joo Rak - Kwon, Yong-Rim - Jo, Woo-Lam - Kim, Myungshin - Kim, Yoo-Jin - Kim, Hongtae - 2024-03-25T10:05:09Z - 2024-03-25T10:05:09Z - 2024-03-22 - 2024-03 -
dc.description.abstract DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41-deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS. -
dc.identifier.bibliographicCitation LEUKEMIA -
dc.identifier.doi 10.1038/s41375-024-02228-4 -
dc.identifier.issn 0887-6924 -
dc.identifier.scopusid 2-s2.0-85188255288 -
dc.identifier.uri -
dc.identifier.wosid 001188807800002 -
dc.language 영어 -
dc.publisher Springer Science and Business Media LLC -
dc.title Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation -
dc.type Article -
dc.description.isOpenAccess TRUE -
dc.relation.journalWebOfScienceCategory Oncology;Hematology -
dc.relation.journalResearchArea Oncology;Hematology -
dc.type.docType Article -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -
dc.subject.keywordPlus DNA-DAMAGE RESPONSE -
dc.subject.keywordPlus DIFFERENTIATION -
dc.subject.keywordPlus LEUKEMOGENESIS -
dc.subject.keywordPlus LEUKEMIA -
dc.subject.keywordPlus REPAIR -
dc.subject.keywordPlus METTL3 -


Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.