The control of the cell cycle with particular emphasis on the G1/S transition

Abstract: Tumour development occurs to a large extent because of dysregulation of the cell cycle. Of particular importance are defects occurring in the G1 phase. The reason why G1 is critical is because of the influence of several signals (external signals as well as cyclins and cdks) on this stage. The G1 phase can be divided into two parts, G1pm and G1ps. Each part has its “own” restriction point which needs to be passed in order to progress to S phase. The first restriction point, R1, is growth-factor dependent and decides if the cell progresses to S phase and hence also controls the chromosomal cell cycle i.e. DNA-replication and mitosis. The second restriction point, R2, located in G1ps is nutrient dependent and decides when the cell will progress to S phase. By doing so it controls that the daughter cells are the same size before they enter S phase. Transformed cells need to overcome both R1 and R2 in order to induce tumour development. Transition from G1 to S is driven by genes that encode several proteins that regulate downstreaming signals. Ras is one of the most important proteins that not only regulate one downstream pathway but several overlapping pathways. Even though the main emphasis is on the G1 phase other phases can also affect the transformation process. For instance unsolved and incompletely replicated DNA in the S phase without a cell cycle stop before M phase is an area that has aroused recent interest. There are several issues that need further investigation. The findings of novel suppressor genes that inhibit oncogene expression and consequently induce apoptosis and cell senescence may contribute to the solving of the cancer riddle.