Cytoskeleton Induces DNA Replication

Advertisement

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 synthesis
(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 replication is also observed in plants; dry tomato seeds are arrested at the G1 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 cytoskeleton 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 microtubules of the cytoskeleton causes activation of the transcription factor NF-kappa B and induces expression of NF-kappa B-dependent genes. Cytoskeleton microtubules 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 filament) 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).

Advertisement