Loss of Dystroglycan Drives Cellular Senescence via Defective Mitosis-Mediated Genomic Instability.

ABSTRACT: Nuclear β-dystroglycan (β-DG) is involved in the maintenance of nuclear architecture and function. Nonetheless, its relevance in defined nuclear processes remains to be determined. In this study we generated a C2C12 cell-based DG-null model using CRISPR-Cas9 technology to provide insights into the role of β-DG on nuclear processes. Since DG-null cells exhibited decreased levels of lamin B1, we aimed to elucidate the contribution of DG to senescence, owing to the central role of lamin B1 in this pathway. Remarkably, the lack of DG enables C2C12 cells to acquire senescent features, including cell-cycle arrest, increased senescence-associated-β-galactosidase activity, heterochromatin loss, aberrant nuclear morphology and nucleolar disruption. We demonstrated that genomic instability is one dr

SUBMITTER: Jimenez-Gutierrez GE 

PROVIDER: S-EPMC7404207 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature