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Genome stability of neurons is essential for proper physiological brain function. Failure in accurate genomic DNA repair can result in abnormal neuronal functions or cell death. Genomic instability has been implicated in increased risks of neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying neuronal genome stability remain poorly understood. Mutations in the <jats:italic>Strawberry Notch Homolog 1<\/jats:italic> (<jats:italic>SBNO1<\/jats:italic>) have been suggested to contribute to these disorders. Here, we investigated the molecular mechanisms underlying histological abnormalities observed in the cortex of <jats:italic>Sbno1<\/jats:italic> knockout (KO) mice. Comprehensive gene expression analysis revealed that <jats:italic>Sbno1<\/jats:italic> KO affects the expression of genes related to cell survival, consistent with the increased apoptosis observed in <jats:italic>Sbno1<\/jats:italic> KO cortices. Among the genes downregulated in <jats:italic>Sbno1<\/jats:italic> KO, we focused on <jats:italic>Yeats4<\/jats:italic>. Overexpression of Yeats4 rescued the accumulation of genomic DNA damage and cell death caused by <jats:italic>Sbno1<\/jats:italic> deletion. These findings suggest that Sbno1 is critical in safeguarding the neuronal genome, at least in part, via regulating <jats:italic>Yeats4<\/jats:italic> expression.<\/jats:p>","DOI":"10.1038\/s41420-025-02640-4","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T16:48:08Z","timestamp":1753375688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Strawberry notch 1 safeguards neuronal genome via regulation of Yeats4 expression"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-1617","authenticated-orcid":false,"given":"Dai","family":"Ihara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Narumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukie","family":"Kande","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuaki","family":"Ikuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1063-5822","authenticated-orcid":false,"given":"Manabu","family":"Shirai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Nitta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3764-6238","authenticated-orcid":false,"given":"Hayato","family":"Naka-Kaneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Katsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"2640_CR1","doi-asserted-by":"publisher","first-page":"dev156059","DOI":"10.1242\/dev.156059","volume":"146","author":"K Obernier","year":"2019","unstructured":"Obernier K, Alvarez-Buylla A. 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