Actin filaments are highly dynamic and their polymerization is usually correlated to their disassembly. Generally, actin filament polymerization occurs over three phases: nucleation, elongation, and steady state phases. During the nucleation phase, the formation of a stable nucleus occurs. This is usually comprised of three actin monomers in complex. In the elongation phase, monomers are rapidly added to the filament at the (+ve) or barbed end and this is often facilitated by additional elongation factors such as formin.
As DNA unwinding and DNA synthesis progresses, the DNA ahead of the replication fork becomes overwound or positively supercoiled. This creates superhelical tension which is usually resolved by enzymes known as topoisomerases. However, the super helical tension is higher in longer chromosomes and in regions of the chromatin tethered to the nuclear envelope. It is now evident that the torsional stress from the replication forks impinge on the nuclear envelope in the form of mechanical signals that recruit ATR, a DNA damage checkpoint protein, independent of its role in DNA repair. ATR may then enable transient detachment of chromatin from the nuclear envelope, thus allowing for the completion of replication. ATR is also recruited during prophase to resolve the topological stress arising from chromatin condensation and is required for coordinating DNA replication and chromatin condensation.
Three main types of phosphoinositides- PIP, PIP2, and PIP3- have important roles in intracellular signaling, lipid signaling, and membrane trafficking; these phosphoinositides differ solely in the number of phosphate groups that are attached by phosphoinositol kinases to their inositol rings. Increased levels of PIP in the plasma membrane greatly reduces the F-actin binding and depolymerizing activity of ADF (actin depolymerizing factor). Increased levels of PIP2 in the plasma membrane inhibits actin filament capping by capping protein and greatly reduces the F-actin binding and depolymerizing activity of ADF. Phosphatidylinositol-3-kinase (PI3K) and PTEN (Phosphatase and tensin homolog) signal transduction pathways regulate the level of PIP3 in response to extracellular guidance cues during filopodia motility. The accumulation of PIP3 in filopodia is suggested to cause actin polymerization and increased cellular movement.