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These structures play important biological functions, such as regulating gene expression and DNA repair. However, when unresolved by nucleic acid processing factors, pathological R-loops can be harmful and lead to genome instability. N6-Methyladenosine (m6A), the most prevalent modification in messenger RNA, has been recently identified to be crucial for regulating R-loop balance and maintaining genome stability. Strikingly, m6A-modified R-loop formation can have opposing consequences, either stabilization or resolution, depending on the biological context. In this review, we discuss the current knowledge of the regulatory roles of m6A on R-loops across various processes, including gene transcription, DNA repair, and\u00a0centromere\u00a0and telomere stability. Additionally, we explore other m6A-mediated processes, such as nascent transcription and chromatin landscape, that potentially affect R-loop dynamics. Finally, we discuss the current limitations and future directions of studying the m6A\u2013R-loop axis, as well as the opportunities to target this pathway as a potential therapeutic strategy.<\/jats:p>","DOI":"10.1093\/narcan\/zcaf022","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:34:05Z","timestamp":1753184045000},"source":"Crossref","is-referenced-by-count":3,"title":["m6A modification in R-loop homeostasis: a potential target for cancer therapeutics"],"prefix":"10.1093","volume":"7","author":[{"given":"Minh-Anh","family":"Vu","sequence":"first","affiliation":[{"name":"Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Universit\u00e9 ,\u00a075005 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic 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