{"title":"草莓notch 1通过调控yeat4的表达来保护神经元基因组。","authors":"Dai Ihara, Ayano Narumoto, Yukie Kande, Tomoki Hayashi, Yasuaki Ikuno, Manabu Shirai, Masaki Wakabayashi, Ryo Nitta, Hayato Naka-Kaneda, Yu Katsuyama","doi":"10.1038/s41420-025-02640-4","DOIUrl":null,"url":null,"abstract":"<p><p>Neurons are subjected to various stresses, including high metabolic demand, physiological activity, and transcriptional regulation, to which their genomic DNA are vulnerable. 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 Strawberry Notch Homolog 1 (SBNO1) have been suggested to contribute to these disorders. Here, we investigated the molecular mechanisms underlying histological abnormalities observed in the cortex of Sbno1 knockout (KO) mice. Comprehensive gene expression analysis revealed that Sbno1 KO affects the expression of genes related to cell survival, consistent with the increased apoptosis observed in Sbno1 KO cortices. Among the genes downregulated in Sbno1 KO, we focused on Yeats4. Overexpression of Yeats4 rescued the accumulation of genomic DNA damage and cell death caused by Sbno1 deletion. These findings suggest that Sbno1 is critical in safeguarding the neuronal genome, at least in part, via regulating Yeats4 expression.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"342"},"PeriodicalIF":7.0000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289961/pdf/","citationCount":"0","resultStr":"{\"title\":\"Strawberry notch 1 safeguards neuronal genome via regulation of Yeats4 expression.\",\"authors\":\"Dai Ihara, Ayano Narumoto, Yukie Kande, Tomoki Hayashi, Yasuaki Ikuno, Manabu Shirai, Masaki Wakabayashi, Ryo Nitta, Hayato Naka-Kaneda, Yu Katsuyama\",\"doi\":\"10.1038/s41420-025-02640-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Neurons are subjected to various stresses, including high metabolic demand, physiological activity, and transcriptional regulation, to which their genomic DNA are vulnerable. 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 Strawberry Notch Homolog 1 (SBNO1) have been suggested to contribute to these disorders. Here, we investigated the molecular mechanisms underlying histological abnormalities observed in the cortex of Sbno1 knockout (KO) mice. Comprehensive gene expression analysis revealed that Sbno1 KO affects the expression of genes related to cell survival, consistent with the increased apoptosis observed in Sbno1 KO cortices. Among the genes downregulated in Sbno1 KO, we focused on Yeats4. Overexpression of Yeats4 rescued the accumulation of genomic DNA damage and cell death caused by Sbno1 deletion. These findings suggest that Sbno1 is critical in safeguarding the neuronal genome, at least in part, via regulating Yeats4 expression.</p>\",\"PeriodicalId\":9735,\"journal\":{\"name\":\"Cell Death Discovery\",\"volume\":\"11 1\",\"pages\":\"342\"},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2025-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289961/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Death Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41420-025-02640-4\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02640-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Strawberry notch 1 safeguards neuronal genome via regulation of Yeats4 expression.
Neurons are subjected to various stresses, including high metabolic demand, physiological activity, and transcriptional regulation, to which their genomic DNA are vulnerable. 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 Strawberry Notch Homolog 1 (SBNO1) have been suggested to contribute to these disorders. Here, we investigated the molecular mechanisms underlying histological abnormalities observed in the cortex of Sbno1 knockout (KO) mice. Comprehensive gene expression analysis revealed that Sbno1 KO affects the expression of genes related to cell survival, consistent with the increased apoptosis observed in Sbno1 KO cortices. Among the genes downregulated in Sbno1 KO, we focused on Yeats4. Overexpression of Yeats4 rescued the accumulation of genomic DNA damage and cell death caused by Sbno1 deletion. These findings suggest that Sbno1 is critical in safeguarding the neuronal genome, at least in part, via regulating Yeats4 expression.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.