De Koninck Magali, Losada Ana
Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid E-28029, Spain.
Cold Spring Harb Perspect Med. 2016 Dec 1;6(12):a026476. doi: 10.1101/cshperspect.a026476.
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.
黏连蛋白是一种大型环状蛋白质复合体，从酵母到人类都保守存在，它参与细胞核中发生的大多数DNA事务。它介导姐妹染色单体黏连，这对染色体分离和同源重组（HR）介导的DNA修复至关重要。分别与诸如CTCF和中介体等结构蛋白和转录调节因子一起，它在不同尺度上对基因组组织有贡献，从而影响转录、DNA复制和基因座重排。尽管黏连蛋白对细胞活力至关重要，但功能的部分丧失在不同细胞类型中可能对这些过程产生不同影响。在几种癌症中已鉴定出编码黏连蛋白亚基和该复合体调节因子的基因突变。了解这些改变的功能意义可能对患者分类、风险预测和治疗选择有相关影响。此外，鉴定携带黏连蛋白突变的癌细胞中的脆弱性可能提供新的治疗机会并指导个性化治疗的设计。
