Response coordination, temporal

Fig. 1. A general framework for the temporal coordination of DNA damage responses. (A) Biological responses to DNA damage occur, temporally, from reversible to irreversible states. (B) Multiple outcomes are organized to depict immediate-early, early, and late responses to DNA dam e, as indicated by shaded boxes (see text for discussion).

We emphasize that the processes depicted in Figure 1 and discussed above are more dynamic than could be presented in a two-dimensional diagram. We would also emphasize that this framework is not a molecular pathway —none of the arrows represent a specific biochemical mechanism. Rather, this framework temporally oig anizes the many cellular responses that have been observed after cells incur DNA damage. In particular, the framework highlights the importance of transitions from reversible to irreversible events and how the status of DNA repair may control these transitions. At the end of the chapter, we will discuss two alternative models for how DNA repair may coordinate the checkpoint and death responses to damage. Before those discussions, we will summarize briefly the current knowledge on several key players in the DNA damage response network. 

VI. Alternative Models for the Temporal Coordination of DNA Damage Responses... 

Fig. 3. Alternative models for the temporal coordination of DNA damage responses. (A) The integrative surveillance (IS) model proposes that signals indicating levels of DNA damage and the progress of repair are integrated by a regulatory hub to either activate or inhibit cell-cycle checkpoints versus apoptosis. The temporal coordination of different biological outcomes is the result of deliberated decisions made by the regulatory hub. (B) The autonomous pathway (AP) model proposes that DNA...

The most likely configuration must surely be a universe in equilibrium, but not necessarily static equilibrium. Furthermore, the assumption of imi-versally uniform distribution of matter is not necessarily correct, as it ignores the symmetry between matter and antimatter. The single most important mathematical difference between matter and antimatter is in their temporal response. Whatever the topology required to accommodate equal amoimts of matter and antimatter, it cannot contain a privileged cosmic time coordinate. 

The apparent contradiction between inflammatory chemokine and chemokine receptor redundancy observed in vitro and specific phenotypes revealed from gene-targeted animals can be resolved if one considers that these chemokines and their receptors function as a cooperative network in vivo to generate a complete immune response. Cooperation exists by coordinating the temporal expression of chemokine receptors on different cell types, the same cell type, or even the same cell. 

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