The emerging role of actin and myosin in the 3D organization of the genome suggests a general role for these cytoskeletal proteins as gate keepers of genome stability and, therefore, integrity. Compatible with this hypothesis, we have recently reported that NM1 associates with the mammalian genome and that loss of NM1 compromises cell cycle progression. We also reported that NM1 association with the chromatin is regulated by the glycogen synthase kinase (GSK) 3β, a downstream effector of several wnt signaling pathways. In the absence of GSK3β, NM1 is polyubiquitinated and degraded via the proteasome route (Figure 3).
We are currently pursuing the hypothesis that actin and NM1 contribute to the architecture of the cell nucleus during the DNA damage response. Ongoing projects aim at understanding whether NM1 promotes genome stability by guarding against the formation of persistent R-loops that are believed to negatively regulate the activation of p53 signaling. We follow a global genome wide approach, in combination with high content phenotypic profiling and superresolution microscopy.