PT - JOURNAL ARTICLE AU - Scheffler, Kathleen AU - Giannini, Federica AU - Mogessie, Binyam TI - The prophase oocyte nucleus is a homeostatic G-actin buffer AID - 10.1101/2020.10.30.353961 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.10.30.353961 4099 - http://biorxiv.org/content/early/2020/10/30/2020.10.30.353961.short 4100 - http://biorxiv.org/content/early/2020/10/30/2020.10.30.353961.full AB - Formation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders, and infertility. We found that oocytes regulate F-actin organisation and function by promptly transferring excess monomeric G-actin from the cytoplasm to the nucleus. Inside healthy oocyte nuclei, transferred monomers form dynamic F-actin structures, a conserved feature that significantly declines with maternal age. Monomer transfer must be controlled tightly. Blocked nuclear import of G-actin triggers assembly of a dense cytoplasmic F-actin network, while excess G-actin in the nucleus dramatically stabilises nuclear F-actin. Imbalances in either direction predispose oocytes to aneuploidy. The large oocyte nucleus is thus a homeostatic G-actin buffer that is used to maintain cytoplasmic F-actin form and function.One Sentence Summary Mammalian oocyte nuclei buffer cytosolic G-actinCompeting Interest StatementThe authors have declared no competing interest.