The Drosophila mei-S332 and ord gene products are essential for proper sist
er-chromatid cohesion during meiosis in both males and females. We have con
structed flies that contain null mutations for both genes. Double-mutant fl
ies are viable and fertile. Therefore, the lack of an essential role for ei
ther gene in mitotic cohesion cannot be explained by compensatory activity
of the two proteins during mitotic divisions. Analysis of sex chromosome se
gregation in the double mutant indicates that ord is epistatic to mei-S332.
We demonstrate that ord is not required for MEI-S332 protein to localize t
o meiotic centromeres. Although overexpression of either protein in a wild-
type background does not interfere with normal meiotic chromosome segregati
on, extra ORD+ protein in mei-S332 mutant males enhances nondisjunction at
meiosis II. Our results suggest that a balance between the activity of mei-
S332 and ord is required for proper regulation of meiotic cohesion and demo
nstrate that additional proteins must be functioning to ensure mitotic sist
er-chromatid cohesion.