Evidence that the spindle assembly checkpoint does not regulate APC^Fzyactivity inDrosophilafemale meiosis

Abstract

The spindle assembly checkpoint (SAC) plays an important role in mitotic cells to sense improper chromosome attachment to spindle microtubules and to inhibit APC(Fzy)-dependent destruction of cyclin B and Securin; consequent initiation of anaphase until correct attachments are made. In Drosophila , SAC genes have been found to play a role in ensuring proper chromosome segregation in meiosis, possibly reflecting a similar role for the SAC in APC(Fzy) inhibition during meiosis. We found that loss of function mutations in SAC genes, Mad2, zwilch, and mps1, do not lead to the predicted rise in APC(Fzy)-dependent degradation of cyclin B either globally throughout the egg or locally on the meiotic spindle. Further, the SAC is not responsible for the inability of APC(Fzy) to target cyclin B and promote anaphase in metaphase II arrested eggs from cort mutant females. Our findings support the argument that SAC proteins play checkpoint independent roles in Drosophila female meiosis and that other mechanisms must function to control APC activity.

How oocytes try to get it right: spindle checkpoint control in meiosis

“…X. laevis oocytes undergo metaphase-to-anaphase transition of meiosis I in the presence of nocodazole, which destabilizes spindles and activates the spindle checkpoint in cells harboring a functional SAC (Shao et al 2013). In D. melanogaster oocytes, loss of checkpoint components does not affect Cyclin B degradation, as expected in the presence of a functional spindle checkpoint (Batiha and Swan 2012).…”

Xenopus oocyte meiosis lacks spindle assembly checkpoint control

“…Mutations in mei-1, mei-2, and zyg-9, which code for components of the oocyte spindle, do not cause metaphase arrest, even though spindles in these oocytes are severely abnormal (Clark-Maguire and Mains, 1994;Matthews et al, 1998). Similarly, mutations in multiple SAC genes do not affect cyclin B changes or chromosome segregation in Drosophila melanogaster oocytes (Batiha and Swan, 2012). However, direct demonstration that complete disruption of meiotic spindle does not cause metaphase arrest, as demonstrated here in frog oocytes, is lacking.…”

Cell Cycle Regulators in Female Meiosis of Drosophila melanogaster

“…Furthermore, loss of Mad2 as well as BubR1, Mps1 and another SAC gene, Zwilch, do not result in reduced levels of the APC/C Fzy target, Cyclin B, either globally or locally on the meiosis I spindle, as would be expected if the APC/C were activated [54]. Genetic evidence also argues against a role for the SAC in inhibiting APC/C activity in the 2nd meiotic division [54].…”

“…Unlike many SAC proteins, Mad2 appears to have no function outside of the SAC [53] and, importantly, null alleles of Mad2, do not result in precocious anaphase in meiosis I [54]. Furthermore, loss of Mad2 as well as BubR1, Mps1 and another SAC gene, Zwilch, do not result in reduced levels of the APC/C Fzy target, Cyclin B, either globally or locally on the meiosis I spindle, as would be expected if the APC/C were activated [54].…”