Growth, Differentiation and Sexuality

sub-apical hyphal cells likely provide a reservoir of
mitotically quiescent nuclei that are somewhat resistant
to the effects of DNA damage (Harris 1997).
Because similar compartments of mitotically inactive
nuclei do not appear to exist in N. crassa and
A. gossypii, these fungi may be more reliant upon
mitotic asynchrony to maintain viability after exposure
to DNA damaging agents.
VII. Coordination of Mitosis
with Branch Formation
The formation of lateral branches is a morphogeneticprocessuniquetofilamentousfungi
(Momany 2002). Several studies have shown that
branch formation is tightly coordinated with
growth (Trinci 1978). For example, new tips
typically form to accommodate the increased
volume of cytoplasm generated under optimal
growth conditions. More recently, it was also
demonstrated that branch formation correlates
with mitosis (Dynesen and Nielsen 2003). In
particular, although the inhibition of mitosis in
A. nidulans using either nimX or nimA mutations
does not affect growth, it clearly prevents the
initiation of new branches. The coordination
of branch formation with mitosis may ensure
the appropriate ratio of cytoplasmic volume per
nucleus is maintained in growing hyphae.
The mechanisms underlying the relationship
between mitosis and branch formation remain an
interesting puzzle. Although mitosis is required
for branching, a recent study suggested that early
events in branch formation might precede mitosis
(Westfall and Momany 2002). Specifically, in
A. nidulans, localization of the septin AspB to the
incipient branch site occurs before the previously
quiescent nuclei reenter mitosis. Moreover, septin
localization persists during the first mitosis, before
finally disappearing as the new branch elongates.
Because septins have a conserved role in cellular
morphogenesis as organizational scaffolds capable
of linking cytoskeletal dynamics with the cell
cycle (Gladfelter et al. 2001), this observation suggests
a potential model for the reciprocal coordination
of mitosis and branch formation (Fig. 3.5).
In particular, septins may provide an anchor for
the localized recruitment of regulatory proteins
that promote mitotic reentry, such as the Cdc25
phosphatase. At the same time, other mitotic regulators
may influence septin organization, thereby
Fungal Mitosis 45
Fig. 3.5.A–D Model for the coordinated regulation of branch
formation and mitosis. A A septin ring forms at the presumptive
branch site (shaded circle). Nuclei remain in G2.
B A signal generated by regulators associated with the septin
ring promotes mitotic entry as the new branch emerges. C
Nuclei undergo mitosis (closed circles) as the new branch
continuestoextend.D The septin ring disassembles, and
post-mitotic nuclear migration into the new branch occurs
modulating cytoskeletal function to prevent commitment
to branch formation if mitosis does not
proceedproperly.Itshouldbepossibletotestthis
speculative model using the tools available for A.
nidulans. More importantly, it will be necessary to
determine if the coordination of branching with
mitosis is a general feature of filamentous fungi,
or if it is limited to only those fungi that, like
A. nidulans, form obviously differentiated hyphal
compartments (Harris 1997).
VIII. Regulation of Mitosis in Response
to DNA Damage and Replication
Stress
A characteristic feature of the DNA damage response
is the activation of checkpoints that block
mitosis when DNA is damaged (Zhou and Elledge
2000). Typically, DNA damage inhibits CDK activation
and causes arrest prior to mitotic entry. Because
A. nidulans possesses two mitosis-promoting
protein kinases, it was of interest to determine how
their respective activities were affected by DNA
damage. As demonstrated by Ye et al. (1997b), exposure
of hyphal cells to DNA damage blocks mitotic