Cells carry out a complex array of metabolic processes that must be regulated in response to a broad spectrum of internal and external factors. Hence, interconvertible enzymes and the enzymes responsible for their interconversion act, not as isolated “on” and “off” switches, but as binary elements within integrated biomolecular information processing networks.
One well-studied example of such a network is the eukaryotic cell cycle that controls cell division. Upon emergence from the G0 or quiescent state, the extremely complex process of cell division proceeds through a series of specific phases designated G1 , S, G2 , and M (Figure 1). Elaborate monitoring systems, called checkpoints, assess key indicators of progress to ensure that no phase of the cycle is initiated until the prior phase is complete. Figure 1 outlines, in simplified form, a chromosome-associated protein kinase called ATM binding to and being activated by regions of chromatin-containing double stranded breaks in the DNA. Upon activation, one subunit of the activated ATM dimer dissociates and initiates a series, or cascade, of protein phosphorylation–dephosphorylation events mediated by the CHK1 and CHK2 protein kinases, the Cdc25 protein phosphatase, and finally a complex between a cyclin and a cyclin-dependent protein kinase, or Cdk. In this case, activation of the Cdk-cyclin complex blocks the G1 to S transition, thus preventing the replication of damaged DNA. Failure at this checkpoint can lead to mutations in DNA that may lead to cancer or other diseases. Additional checkpoints and signaling cascades (not shown) interact together to control cell cycle progression in response to multiple indicators of cell status.
Fig1. A simplified representation of theG1 to S checkpoint of the eukaryotic cell cycle. The circle shows the various stages in the eukaryotic cell cycle. The genome is replicated during S phase, while the two copies of the genome are segregated and cell division occurs during M phase. Each of these phases is separated by a G, or growth, phase characterized by an increase in cell size and the accumulation of the precursors required for the assembly of the large macromolecular complexes formed during S and M phases.
