Cell cycle checkpoints

Cell cycle checkpoints are control mechanisms that regulate cell division and prevent cells from continuing through the cycle if the events of the preceding phase have not been completed. The main control points in mammals are:

•       At the end of G1 phase (restriction point) the cell checks the quality of the DNA, the presence of specific growth factors (p.e. fibroblast growth factor) and cell size. Arrest at that checkpoint allows repair of damaged DNA before the cell enters the replication phase. If DNA can’t be repair the cell induces apoptosis. The phase of arrest in which the cell doesn’t continue its cycle is G₀. This checkpoint is controlled by Cyclin D-CDK 4/6 and Cyclin E-CDK 2;
•          At the S phase, continual control of the integrity of DNA allows that mutated bases are not replicated and the repair of possible errors that occur during replication. The proteins involved in this damage detection are DNA pol ε, PCNA and RFC. This checkpoint is controlled by Cyclin A-CDK 2;
•          At the end of G2 phase , cells check if there are conditions for mitosis (cell size, quality of DNA and existence of nutrients necessary for the mitotic phase) and prevent the initiation of mitosis before DNA replication is completed and until there are conditions for cell division (cell size and existence of necessary nutrients). If there are no conditions, cells enter in a quiescent state where DNA repair or apoptosis can occur. This checkpoint is controlled by Cyclin A-CDK1;
•     At the beginning of anaphase, spindle assembly checkpoint stops mitosis if the chromosomes are not well aligned and its centromeres are not properly attached to the microtubules and thus, not prepared for equal distribution. This checkpoint is controlled by the anaphase-promoting complex/cyclosome (APC/C).
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Fig.1 The cell cycle checkpoints.

In case of a failure in these checkpoints, cells with damaged DNA can proliferate at higher rates than normal cells, becoming neoplasic.

For this reason the studies of these checkpoints in the cell cycle are important for the production of new drugs in the treatment of problems like  cancer.

GEOFFREY M. COOPER, ROBERT E. HAUSMAN , (2007). THE CELL: A Molecular Approach . 4th ed. e.g. England. Sunderland (MA): Sinauer Associates.