Nuclear Actin Polymerized by mDia2 Confines Centromere Movement during CENP-A Loading

Centromeres are specialized chromosomal regions epigenetically defined by the histone H3 variant centromere protein A (CENP-A). CENP-A needs to be replenished in every cell cycle, but how new CENP-A is stably incorporated into centromeric chromatin remains unclear. We have discovered that a cytoskeletal protein, diaphanous formin mDia2, is essential for the stable incorporation of new CENP-A proteins into centromeric nucleosomes. Here we report that mDia2-mediated formation of dynamic and short nuclear actin filaments in G1 nucleus is required to maintain CENP-A levels at the centromere. Importantly, mDia2 and nuclear actin are required for constrained centromere movement during CENP-A loading, and depleting nuclear actin or MgcRacGAP, which lies upstream of mDia2, extends centromeric association of the CENP-A loading chaperone Holliday junction recognition protein (HJURP). Our findings thus suggest that nuclear actin polymerized by mDia2 contributes to the physical confinement of G1 centromeres so that HJURP-mediated CENP-A loading reactions can be productive, and centromere's epigenetic identity can be stably maintained.