Appendix 1A Molecular Interaction Maps of DNA Replication

Researchers interested in DNA replication and cell cycle control need useful tools to integrate a large collection of molecular data in a clear and standardized format. Here we demonstrate the use of one such tool—the Molecular Interaction Map (MIM). MIM is a graphical representation that unambiguously represents signal transduction pathways and molecular networks in a way that facilitates viewing multiple interactions of a single molecule at a single location on the map. Furthermore, an interactive electronic MIM (eMIM) allows the user to navigate through the molecular interaction network and link directly to molecular databases, references, and annotations that contain pertinent information. The interested researcher can read the annotations to gain in-depth information on each molecular interaction, or browse the various maps to become acquainted with the general concept of how cells regulate a particular metabolic process. MIMs and eMIMs depicting DNA replication and cell-cycle processes, as they are currently understood, are described in detail in the cited literature and are accessible on the Web at http://discover.nci.nih.gov/mim. Investigators often describe biochemical pathways in cartoon-like diagrams that are sometimes incomplete and ambiguous. For example, an arrow between two components could signify either an increase in quantity, an increase in activity, a chemical conversion, or an enzymatic action. These rich interconnections often involve extensive protein–protein interactions and protein modifications that make these networks difficult to diagram with precision. For example:Enzymes in the cell-cycle-regulatory network (e.g., kinases) are often substrates of other enzymes. Molecules are often subject to modifications...