LACK OF CHECKPOINT CONTROL AT THE METAPHASE ANAPHASE TRANSITION - A MECHANISM OF MEIOTIC NONDISJUNCTION IN MAMMALIAN FEMALES/

A checkpoint mechanism operates at the metaphase/anaphase transition t o ensure that a bipolar spindle is formed and that all the chromosomes are aligned at the spindle equator before anaphase is initiated. Sinc e mistakes in the segregation of chromosomes during meiosis have parti cularly disastrous consequences, it seems likely that the meiotic cell division would be characterized by a stringent metaphase/anaphase che ckpoint. To determine if the presence of an unaligned chromosome activ ates the checkpoint and delays anaphase onset during mammalian female meiosis, we investigated meiotic cell cycle progression in murine oocy tes from XO females and control siblings. Despite the fact that the X chromosome failed to align at metaphase in a significant proportion of cells, we were unable to detect a delay in anaphase onset. Based on s tudies of cell cycle kinetics, the behavior and segregation of the X c hromosome, and the aberrant behavior and segregation of autosomal chro mosomes in oocytes from XO females, we conclude that mammalian female meiosis lacks chromosome-mediated checkpoint control. The lack of this control mechanism provides a biological explanation for the high inci dence of meiotic nondisjunction in the human female. Furthermore, sinc e available evidence suggests that a stringent checkpoint mechanism op erates during male meiosis, the lack of a comparable checkpoint in fem ales provides a reason for the difference in the error rate between oo genesis and spermatogenesis.