Cell Cycle/DNA Damage

The cell cycle is a regulatory system that controls the proper order and timing of cellular growth and division events. Mutation in the proteins regulating the cell cycle, leads to uncontrolled cell division or propagation of damaged DNA which contributes to genomic instability and oncogenesis.

The cell cycle is consisted of 4 main phases: Gap 1 (G1), DNA replication (S), Gap 2 (G2), and mitosis (M). There are “checkpoints” mechanism regulates the transition between these phases, at the G1/S boundary, in the S-phase and during G2/M phases. Cell can only pass through these checkpoints when signaling factors are activated and free of DNA damage. Important proteins that control cell cycle events and checkpoints are cullins, cyclins, cyclin-dependent kinases (Cdks), p53 and their inhibitors etc. Cdks family (Cdk2, Cdk3, Cdk4 and Cdk6) are Ser/Thr kinases that regulate cell cycle progression in association with cyclin binding partners (cyclin D, cyclin E and cyclin A) during all four phases. p53 halts the cell cycle if the DNA is damaged and allowing time for DNA repair to progress; it can also initiate apoptosis if DNA damage is too severe to be repaired.