NIH Research Festival
FARE Award Winner
During mitosis, nuclear envelope breakdown (NEBD) allows faithful segregation of the duplicated chromosomes. The nuclear envelope (NE) reforms at the end of mitosis, generating a single nucleus in each daughter cell. Polo-like kinase 1 (Plk-1) is a conserved kinase involved in multiple steps of mitosis but it has not been shown to be required for NEBD. We found that in C. elegans embryonic cells partial inactivation of Plk-1 in a temperature-sensitive (ts) mutant animal causes the formation of two nuclei, containing either the maternal or paternal chromosomes, in each daughter cell. These two nuclei give rise to paired nuclei in subsequent cell divisions. This is accompanied by defects in chromosome congression and alignment of the maternal and paternal metaphase plates relative to each other. If NEBD defect in plk-1(ts) cells was due to a defect in disassembly of one or more NE components, then a reduction in NE components by RNAi would facilitate NEBD and re-establish a single nucleus in plk1(ts) cells. Indeed, our data show that reducing certain NPC components rescues the paired-nuclei phenotype in plk1(ts) cells. Moreover, we found that during the first mitosis NEBD is linked to metaphase chromosome alignment, which fails to occur in the plk1(ts) mutant and is rescued by the aforementioned RNAi treatment. Thus, Plk1 may contribute to the first embryonic NEBD by facilitating metaphase chromosome alignment and/or by directly promoting NEBD. In summary, our study uncovered a novel involvement of Plk1 in NEBD and single nucleus formation following fertilization in an intact organism.
Scientific Focus Area: Cell Biology
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