Role of the Centromere/Kinetochore in Cell Cycle Control

Sera from autoimmune patients with anticentromere antibodies (ACAs) recognize a family of three structurally related human centromere proteins. Immunoelectron microscopy shows that these proteins are distributed throughout the heterochromatin subjacent to, and surrounding, the kinetochore. IgGs purified from these sera (ACA-IgG) disrupt mitotic events when microinjected into tissue-culture cells. The phenotype observed depends on the cell cycle position at the time of injection. When cells are injected from prophase onward, there is no apparent disruption of the subsequent mitosis. When cells are injected during the G1 and S phases of the cell cycle, they subsequently become arrested at prometaphase. When ACA-IgGs are introduced into the nucleus during the G2 phase of the cell cycle, the chromosomes successfully complete prometaphase but then remain blocked in metaphase for several hours. These observations define two execution points for antibody action: the S/G2 transition and the onset of prophase. The fact that ACA-IgGs...