Mechanisms of cohesin regulation in vertebrates

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Abstract In vertebrate cells the cohesin protein complex plays critical roles in nuclear structure and function. It tethers together the identical products of DNA replication, called sister chromatids, until cell division and it also mediates intra-chromosomal bridging interactions, forming chromosome loops and domains. While cohesion between sister chromatids is critical for accurate chromosome segregation and certain kinds of DNA repair, the compaction of chromosomes into loops and domains is essential for proper transcription and normal development. How these different kinds of cohesion differ at the molecular level, the mechanisms that ensure each outcome, and the amount of overlap between them are not well understood. Using molecular genetic approaches, we are testing the impacts of specific interactions, in multiple experimental systems, on cohesin regulation. In this application we are requesting supplemental funds to purchase chromatography equipment that will enhance our efficiency in purification and characterization of proteins to complete the projects described in the parent proposal.