Aurora kinases beyond centrosomes : role of transcription factors' phosphorylation in gene expression and cell cycle

Abstract

From Birth to Rebirth, every living cell progress through a defined set of well regulated events that constitute the “Cell Cycle”. This complex and well coordinated set of events with an accurate and precise control in creating a copy of its own is referred to as the cell division cycle. One of the most common means by which mammalian somatic cells divide is by “Mitosis”. The Mitotic cell cycle comprises of totally five parts, two phases S and M, which are the most active phase with two gap phases G1 and G2, separating these two phases and a resting or quiescent phase called G0 phase. Proteins required for increasing the cell size and replicating DNA are synthesised during G1 phase followed by S phase where the genomic DNA is doubled. Following this phase ensues the second gap phase G2 where the cell prepares itself before it is committed to the phase of segregation and division called as the mitotic phase or M phase. During this phase the doubled genetic material condenses to form chromosomes, which align over the equatorial region to finally get segregated into the two identical daughter cells. In order to ensure the faithful segregation of genetic material to the next generation the whole process needs to be constantly monitored. Hence every entry and exit points in the various phases of cell cycle are controlled by dedicated checkpoint machinery that exist within each cell. These control mechanisms basically exist at two levels. Firstly, at the level of switching a resting cell i.e. G0 phase to G1 and subsequent phases of the cycle. This first layer of control is affected generally by factors external to the cell. The second layer is an internal quality control checkpoint system. In general there are three major checkpoints involved during cell cycle, namely G1 checkpoint, G2 checkpoint and M phase checkpoint. These checkpoints ensure correct transmission of genetic information during cell division by constant surveillance for the appearance of any chromosomal aberrations and checking the completeness of events that had occurred in the previous phase. Checkpoints take place towards the end of each phase of mitosis and must be passed before signalling to proceed further and enter into next stage. If errors are sensed during this, the rescue mechanisms try to operate in correcting them and simultaneously try to arrest the cell growth and not progress until repair. For example, a cell is normally prevented to progress from the G1 phase into S phase if it has errors, or mutations, in its genome. The most common defects are the DNA damage and defective spindle alignment which are sensed by the DNA damage checkpoint proteins and the Spindle Assembly checkpoint proteins respectively. If the damage is sensed as irreparable, the cell is directed towards apoptosis, or programmed cell death (Elledge, S.J., 1996).