Cell Cycle Regulated Gene Expression in Yeasts - Advances in Genetics - page 60

The associated binding partner toMcm1p that controls G2-M transcrip-
tion was first characterized biochemically, and named Swi five factor (SFF), with
two forkhead-like transcription factors, Fkh1p and Fkh2p, and another protein
Ndd1p, subsequently identified as important components (Jorgensen and Tyers,
2000, 2004; Knapp

,
2000). The two forkhead transcription factors are required to ensure correct gene
expression at the G2-M interval (Boros

et al. , 1996; Koranda et al. , 2000; Pic et al. , 2000; Zhu et al.

et al. , 2003; Darieva et al. , 2003;

Hollenhorst et al. , 2000, 2001; Kumar et al. , 2000; Lim et al. , 2003; Reynolds

et al. , 2003). Both bind to forkhead DNAmotifs present in the promoters of genes

in the CLB2 cluster. The two proteins are partially redundant, though they appear
to have separate and distinct roles. Fkh2p binds to Mcm1p on gene promoters,
whereas Fkh1p binds in the absence of Mcm1p, with changes in DNA conforma-
tion thought to be important for the recruitment of SFF to promoter DNA.
Transcriptional activation is not imparted through changes in binding of
either Mcm1p or Fkh2p to promoter DNA, as both remain in contact throughout
the cell cycle. Instead, another transcription activator, Ndd1p, has an important
role in this process (Koranda , 1999). Ndd1p is required for

G2-M transcription, with it binding to CLB2 cluster gene promoters dependent
on Fkh2p and Mcm1p. Ndd1p protein levels peak in S and G2 phases, through
both regulation of its transcription and protein stability. Importantly, binding of
Ndd1p to promoters is controlled by the regulated phosphorylation of Fkh2p by
the Clb5p-Cdc28p CDK complex (Pic-Taylor

et al. , 2000; Loy et al.

, 2004). Once Ndd1p is bound
to Fkh2p, this interaction is stabilized by another CDK complex, Clb2p-Cdc28p,
phosphorylating Ndd1p on threonine 319 and resulting in it binding specifically
to the FHA domain of Fkh2p. The complex of Ndd1p-Fkh2p-Mbx1p results in
the transcription of

et al.

, thus creating a positive feedback loop.
Ndd1p is also directly phosphorylated on serine 85 by another cell cycle protein
kinase, the polo-like kinase encoded by the

CLB1 and CLB2

gene, which is required for the
normal temporal expression of the CLB2 cluster (Darieva

CDC5

, 2006). Part of this
mechanism occurs through Cdc5p binding specifically to promoter DNA at the
time when it activates Ndd1p. As

et al.

is part of the CLB2 cluster, this process
offers yet another positive feedback mechanism to control its expression.
A separate layer of control involving protein stability appears to also
operate, at least for one gene in the CLB2 cluster,

CDC5

. This occurs through
Cks1p recruiting the proteasome to its promoter, which results in gene expres-
sion at G2-M (Morris

CDC20

, 2003; Temp ´ et al. et al. , 2007; Yu et al. , 2005).

4. M-G1 waves
Two waves of gene expression occur late in the budding yeast cell cycle and are
controlled by two different transcription systems. One of these involves Mcm1p
along with two homeodomain proteins, Yox1p and Yhp1p, and the other the
Swi5p/Ace2p transcription factor pair.