Nuclear Actin and Genome Organization

Type of Award: Catalyst
Date Awarded: February 2013
Award End Date: January 2015
Amount Awarded: $ 200,000.00
PI(s): Primal de Lanerolle, PhD, UIC; Steven T. Kosak, PhD, NU;

Abstract: Why are there no actin filaments in the nucleus? Actin filaments are rampant in the cytoplasm and the concentration of actin in the nucleus is well-above the concentration needed for the spontaneous polymerization of actin. Still, nuclear actin does not normally polymerize into filaments. The presence of actin in the nucleus was first described in 1967 and the absence of nuclear actin filaments (NAFs) has bedeviled cell biologists since then. We may have the answer to this paradox. We have found that actin filaments, which form in the nucleus in certain pathological conditions, change the structure of DNA. Therefore, the objective of this proposal is to lay the foundation for understanding how NAFs alter genome organization and what this means in terms of the health and survival of cells. Results from these experiments may yield critical insights into the physiological role of nuclear actin in defining genome form and function and how this role is abrogated in diseases, especially neurodegenerative disorders that are associated with NAFs.