DNA Methylation: Key to Cancer Cell Senescence

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This study explores the effects of DNA methylation loss, focusing on DNMT1 and UHRF1 degron alleles to separate methylation impacts from DNA damage. Methylation loss induces senescence marked by G1 arrest, SASP activation, and mechanisms influenced by cGAS and cytoplasmic p21. Findings show UHRF1 loss triggers rapid senescence independently of DNA damage and involve changes in gene expression, promoter activity, and L1 elements. Validation in cell lines and xenografts underscores therapeutic...