Our findings suggest that after exposure to ionizing radiation nearly all DSBs are efficiently rejoined, sometimes resulting in lasting rearrangements of chromatin, but not leaving persistently unrepaired DSBs. DSBs are an extremely severe form of DNA damage that pose a considerable risk to both genetic and epigenetic integrity. DSB-induced genomic instability and the multistage acquisition of mutations conducive to malignant transformation are frequent hallmarks of cancer. NHEJ, which is commonly employed in response to radiation-induced DNA damage, is known to be mutagenic because ends are processed and joined without a homologous template. Perturbed epigenetic regulation is another essential characteristic of cancer. Severe disruptions of chromatin structure, such as those associated with DSBs, are known to facilitate damage-specific epigenetic responses, potentially resulting in epigenetic regulatory defects with serious implications for gene expression. It is therefore conceivable that persistent, radiation-induced 53BP1 clusters may represent memories of past insults, which could constitute an epimutation transmissible over multiple cell generations. Considering the critical importance of chromatin organization in regulation of gene expression, proper restoration of epigenetic patterns Trichostatin A 58880-19-6 following DSB damage would be crucial to avoid perturbation of transcriptional programs involved in activation or silencing of genes, particularly if these had proto-oncogene or tumor suppressor functions. Future studies should focus on evaluating the diverse chromatinremodeling processes involved in DSB repair and whether incomplete or incorrect chromatin remodeling might be associated with DSB-induced epigenetic damage and the perturbation of transcriptional programs. The complexity of the cell cycle is apparent to anyone attempting to teach it, describe it, or model it. From one point of view, the cycle is a series of ordered chemical reactions, regulated by feedback and feedforward control systems that are also chemical reactions. For most investigators, the control system is the interesting part of the cell cycle. The number of chemical reactions involved is very large and due to the enzymatic and spatiotemporal nature of these reactions, the complexity is vastly larger. This level of information requires databases and informatics, and the complexity of the network of reaction pathways suggests the need for mathematical models to enable or facilitate system-wide understanding of cell cycle regulation. Models based on systems of ordinary differential equations have been developed previously and provide a foundation for larger, more accurate models, e.g.. Measurement of the relative expression of cell cycle regulated epitopes in asynchronous cell populations by cytometry produces data from which relative expression over relative time can be extracted. The general value of this is that, given the appropriate set of markers, the shape or profile of expression over the cycle for any epitope can be evaluated within the context of any others.