Revealing the secrets of the Eco1 zinc finger

Cohesin complex is best known to mediate two functions. It ensures the equal segregation of chromosomes during mitosis, and involved in the repair fedility of DNA double strand break. The acetyltransferase Eco1 is a key regulator of cohesin in both processes. During cell cycle, Eco1 acetylates the Smc3 cohesin subunit to induce its chromatin tethering activity. In response to DNA double strand break, Eco1 acetylates another cohesin subunit, Mcd1 which leads to cohesin loading next to the break site. However, the molecuar basis of these different substrate specificity of Eco1 is elusive. Eco1 contains a single C2H2 zinc finge domain. While zinc fingers are best known for their DNA binding activity, we hypothesized that the Eco1 zinc-finger is used to interact with its substrates and determine its specificity. We performed an alanine scan in the zinc-finger domain and examined the effect of each mutation on cells viability. We identified critical residues for its cohesin regulation activity. Interestingly we pinpointed residues that are specific for Eco1 activitiy in either sister chromatid cohesion and DNA repair. Based on the scan results we were able to develop a structural model for Eco1-Smc3 interactions. Our work assign molecular function of Eco1 zinc finger and its non-canonical function in mediating protein-protein interaction. Furthermore, contributes to the understanding how Eco1 and cohesin cooperates in safeguarding genome stability.