Cohesin subunits are frequently mutated in cancer, but how they function as tumor suppressors is unknown. Cohesin mediates sister chromatid cohesion, but this is not always perturbed in cancer cells. Here, we identify a previously unknown role for cohesin. We find that cohesin is required to repress transcription at DNA double-strand breaks (DSBs). Notably, cohesin represses transcription at DSBs throughout interphase, indicating that this is distinct from its known role in mediating DNA repair through sister chromatid cohesion. We identified a cancer-associated SA2 mutation that supports sister chromatid cohesion but is unable to repress transcription at DSBs. We further show that failure to repress transcription at DSBs leads to large-scale genome rearrangements. Cancer samples lacking SA2 display mutational patterns consistent with loss of this pathway. These findings uncover a new function for cohesin that provides insights into its frequent loss in cancer.
Pubmed ID: 30554942 RIS Download
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Database to store and display somatic mutation information and related details and contains information relating to human cancers. The mutation data and associated information is extracted from the primary literature. In order to provide a consistent view of the data a histology and tissue ontology has been created and all mutations are mapped to a single version of each gene. The data can be queried by tissue, histology or gene and displayed as a graph, as a table or exported in various formats.
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* Samples entered include benign neoplasms and other benign proliferations, in situ and invasive tumours, recurrences, metastases and cancer cell lines.
Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
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View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LNCaP is a Cancer cell line with a species of origin Homo sapiens (Human)
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