Cohesin Mutations in Cancer.
Cohesin is a large ring shaped protein complex, conserved from yeast to human, which participates in most DNA transactions that take place in the nucleus. It mediates sister chromatid cohesion, which is essential for chromosome segregation and homologous recombination (HR) mediated DNA repair. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement. Although cohesin is essential for cell viability, partial loss of function can affect these processes differently in distinct cell types. Mutations in genes encoding cohesin subunits and regulators of the complex have been identified in several cancers. Understanding the functional significance of these alterations may have relevant implications for patient classification, risk prediction, and choice of treatment. Moreover, identification of vulnerabilities in cancer cells harboring cohesin mutations may provide new therapeutic opportunities and guide the design of personalized treatments.
Cold Spring Harbor perspectives in medicine