The Endoreduplication Cell Cycle: Regulation and Function 81
et al. 2004), where it was found to be present as two distinct genes (Fulop et al.
2005). The analysis of CSS52A during root nodule development indicated that
this protein plays a key role in the switch from a mitotic to an endoredupli-
cation cell cycle as cells differentiate, rather than in sustaining or enhancing
endoreduplication in differentiated cells.
Thebest-knownfunctionoftheAPC/Cistopromotetheseparationof
sister chromatids, by activating separase activity at metaphase. Since en-
doreduplicated chromosomes are often polytenic, it will be interesting to
learn whether this aspect of APC/C activity is affected in endoreduplicat-
ing cells. Recent investigation in human cells has shown that oscillations in
APC/C activity are part of a redundant pathway that regulates pre-RC for-
mation and rereplication (Machida and Dutta 2007), primarily by the degra-
dation of CycA and geminin in late M-phase and in G1. Plants do not have
geminin orthologs, but low CycA levels are required for endoreduplication in
someArabidopsiscell types (Imai et al. 2006; Yoshizumi et al. 2006). Future
investigation undoubtedly will focus on the role that APC/C may play in CycA
downregulation in endoreduplicating plant cells.
2.4
The Role of CDKs
CDKs are the main workhorses of the cell cycle, and not surprisingly they play
important roles in endoreduplication. CDKs are regulated at different levels,
such as by the time and specificity of their interaction with cyclin partners
(which in turn involves factors controlling the availability of cyclins, such as
cyclin synthesis, degradation, and compartmentalization), by phosphorylation
and dephosphorylation events, and by interaction with specific inhibitors.
A consensus view has emerged from studies of animals and plants, accord-
ing to which the endoreduplication cell cycle involves sustained or upregulated
S-phase CDKs and downregulation of M-phase CDKs (Sauer et al. 1995;
Edgar and Orr-Weaver 2001; Larkins et al. 2001). However, specific CDKs
may have distinct roles in regulating endoreduplication in different species,
or even different cell types in the same organism. For example, in mammalian
trophoblasts, endoreduplication involves loss of CycB expression, and a coinci-
dental increase in CycA- and CycE-associated CDK activity that oscillates prior
to and during S-phase (MacAuley et al. 1998; Hattori et al. 2000). InDrosophila
embryos, CycA and B are present at constant levels, and cdc2 activity is consti-
tutively high. In this system, oscillations of CycE activity and downregulation
of the APC/C trigger endoreduplication. However, these differences may reflect
the specific modes by which endoreduplication occurs in the two examples
above, which differ significantly from the reiterated rounds of gap and com-
plete DNA synthesis phases that define the prototypical endoreduplication cell
cycle discussed in this chapter. In fact, endoreduplicating trophoblasts still
display vestigial aspects of mitosis, whereas endoreduplication inDrosophila