Control Systems in the Living World - Building the Most Complex Structure on Earth - page 24

Cytoskeleton Induces DNA Replication
“The regulation of DNA replication cannot be explained at a genetic level alone,”
according to Casas-Delucchi and Cardoso (2011) . More than a quarter of a century
ago, it was observed that drugs doing the depolymerization of microtubules induce
DNA synthesis, and the reverse is also true: drugs that stabilize the structure of
microtubules block DNA synthesis ( Thyberg, 1984 ). An increase in the number of
microtubules and intermediate filaments in culture induces DNA and protein synthe-
sis ( Palmberg et al., 1985 ) and polymerization of microtubules is involved in cell
proliferation ( Ball et al., 1992 ).
A similar relationship between microtubules and the beginning of DNA replica-
tion is also observed in plants; dry tomato seeds are arrested at the G 1 phase of the
cell cycle, but after imbibition, seeds show an increase in tubulin and DNA content
that is immediately followed by seed germination ( de Castro et al., 1995 ). Under
mild heat stress, microspores in culture rearrange the microtubules of their cytoskel-
eton and start DNA synthesis, thus entering the cell cycle ( Dubas et al., 2011 ).
These and other similar facts led investigators to the idea that microtubules of the
cytoskeleton are involved in DNA replication and cell proliferation in eukaryotes.
Cytoskeleton Regulates Gene Expression
Rosette and Karin (1995) observed that experimental depolymerization of the micro-
tubules of the cytoskeleton causes activation of the transcription factor NF-kappa
B and induces expression of NF-kappa B-dependent genes. Cytoskeleton microtu-
bules in the ciliated protozoan ( Tetrahymena thermophyla ) inhibit the expression
of the gene for one type of β-tubulin, and it seems that microtubules of cilia inhibit
both types of tubulin genes ( Gu et al., 1995 ). The cytoskeleton is also involved
in the localization and translation of specific mRNAs in HeLa cells ( Hesketh and
Pryme, 1991 ).
Evidence shows that cytoskeletal dynamics may regulate genome activity ( Olson
and Nordheim, 2010 ). Experimental reorganization of the cytoskeleton induces
expression of the urokinase-type plasminogen activator (uPA) gene ( Leeet al., 1993 ),
and disruption of the actin microfilament structure (another type of cytoskeleton fila-
ment) in normal rat kidney cells with cytochalasin D induces expression of the PAI-1
(plasminogen activator type-1) gene ( Providence et al., 1999 ). Similar microtubule
effects on gene expression are also observed in apoptotic genes ( Chen et al., 2003 )
and other genes in multicellulars ( Bounoutas et al., 2011 ).
Microtubules of Spindle Poles Regulate Chromosome Segregation
In unicellular eukaryotes, after duplication of chromosomes, sister chromatids must
be separated and the precise transport of the complete set of chromosomes to two
“daughters” must occur. This is not an easy task: “The challenge for the cell is to
compact the genome so that the DNA strands do not become entangled or broken