Cj. Loy et al., NDD1, a high-dosage suppressor of cdc28-1N, is essential for expression ofa subset of late-S-phase-specific genes in Saccharomyces cerevisiae, MOL CELL B, 19(5), 1999, pp. 3312-3327
cdc28-1N mutants progress through the G(1) and S phases normally at the res
trictive temperature but fail to undergo nuclear division. We have isolated
a gene, NDD1, which at a high dosage suppresses the nuclear-division defec
t of cdc28-1N. NDD1 (nuclear division defective) is an essential gene. Its
expression during the cell cycle is tightly regulated such that NDD1 RNA is
most abundant during the S phase, Cells lacking the NDD1 gene arrest with
an elongated bud, a short mitotic spindle, 2N DNA content, and an undivided
nucleus, suggesting that Its function is required for some aspect of nucle
ar division. We show that overexpression of Ndd1 results in the upregulatio
n of both CLB1 and CLB2 transcription, suggesting that the suppression of c
dc28-1N by NDD1 may be due to an accumulation of these cyclins. Overproduct
ion of Ndd1 also enhances the expression of SWI5, whose transcription, like
that of CLB1 and CLB2, is activated in the late S phase. Ndd1 is essential
for the expression of CLB1, CLB2, and SWI5, since none of these genes are
transcribed in its absence. Both CLB2 expression and its upregulation by ND
D1 are mediated by a 240-bp promoter sequence that contains four MCM1-bindi
ng sites. However, Ndd1 does not appear to be a component of any of the pro
tein complexes assembled on this DNA fragment, as indicated by gel mobility
shift assays. Instead, overexpression of NDD1 prevents the formation of on
e of the complexes whose appearance correlates with the termination of CLB2
expression in G(1), The inability of GAL1 promoter-driven CLB2 to suppress
the lethality of NDD1 null mutant suggests that, in addition to CLB1 and C
LB2, NDDI may also be required for the transcription of other genes whose f
unctions are necessary for G(2)/M transition.