Evolutionary significance of G1/S checkpoint among Eukaryotes

Keng Hwa Tan1, Pawan Dhar2
1eric@bii.a-star.edu.sg, BioInformatics Institute; 2pk@bii.a-star.edu.sg, BioInformatics Institute

The highly conserved topology of the cell cycle across an evolutionary spectrum has encouraged formation of a generic model of the cell cycle. The need to create such a model is particularly felt in view of the similarity in the sequential order of events and the inter-molecular interactions. Regulation of cell cycle is vital in maintaining the integrity of hereditary genetic material. Of many checkpoints that enable a statistical precision of stages of the cell cycle, the G1/S in particular plays a pivotal role during early stages of the cell cycle. Progression through G1/S boundary is controlled by a series of internal sensors, commonly called G1/S regulators. Though there has been a significant improvement in the understanding of individual events a complete knowledge of G1/S anatomy is far from over. In certain organisms the gap phases are highly reduced or even completely absent. Thus, it is important to understand the global and local constraints that control the length of gap phases and ‘phase switch’ from G1 to S.

Through the present study, we hope to explore the role of cell cycle control elements of G1/S boundary and to identify critical targets of cyclin dependent kinases. To tackle this big picture, the DNA and protein sequences of G1/S regulators from Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus and Homo sapiens obtained from NCBI and Swiss-Prot databases are currently being compared. We are using bioinformatics pattern matching approaches like ClustalW and T-COFFEE to identify similar molecular regions across species. Phylogenetic analysis and visualization of the ‘closeness’ of the molecules will be performed using PHYLIP and TreeView respectively. Our final aim is to create a universal genetic model that helps in the identification of (a) elementary modes in the cell cycle, (b) distribution of control and (c) new drug targets for apoptosis and cancer.