Cohesin organization, dynamics, and subdomain functions revealed by genetic suppressor screening

Cohesin is a heteropentameric protein complex that contributes to various aspects of chromosome structure and function, such as sister chromatid cohesion, genome compaction, and DNA damage response. Previous studies have provided abundant information on architecture and regional structures of the cohesin complex, but the configuration and structural dynamics of the whole cohesin complex are still largely unknown, partly due to flexibility of its coiled coils. We studied cohesin organization and dynamics using in vivo functional mutation compensation. Specifically, we developed and applied genetic suppressor screening methods to identify second mutations in cohesin complex genes that rescue lethality caused by various site-specific abnormalities in the cohesin complex. Functional analysis of these missense suppressor mutations revealed novel features of cohesin. Here, we summarize recent genetic suppressor screening results and insights into: 1) cohesin's structural organization when holding chromosomal DNAs; 2) interaction between cohesin head-kleisin and hinge; 3) ATP-driven cohesin conformational changes for genome packaging.