Much work remains to characterize the EF complexes that form following DNA damage and their roles in regulating transcription and DNA repair.The mechanism by which EF promotes the recruitment of repair factors to sites of damage remains poorly understood.Although direct binding to some repair proteins could be involved, it is quite likely that modication of chromatin structure plays an important role in the ability of EF to stimulate DNA repair.How the interaction between EF and GCN, and perhaps other chromatinmodifying enzymes, is regulated in response to DNA damage is another area of research that needs to be addressed.Finally, the physiologic relevance of EF in the response to DNA damage remains to be established.EF can behave as either an oncogene or a tumor suppressor gene in mouse models, depending on the experimental context.An alternative explanation is that EF suppresses tumor development by enhancing DNA repair efciency and maintaining genomic stability.Given that radiotherapy and many chemotherapeutic drugs function by causing DNA damage, it will also be of interest to determine how EF modulates the response to cancer therapies by either enhancing repair and cancer cell survival or promoting apoptosis and tumor regression.A cooperative activation loop among SWISNF, gammaHAX and H acetylation for DNA doublestrand break repair.Access the most recent version of this article at: doi. Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from cancerres.aacrjournals.org on September. American Association for Cancer Research. Conversely, inactivation of both wee and cdc abolishes checkpoint control.Therefore, there is an intense interest to understand checkpointsignalling pathways, and in particular to decipher how these pathways interface with the core cell cycle regulators.Among these is an inhibitory tyrosine phosphorylation on tyrosine tyrosine kinases.Further, the substitution of a nonphosphorylatable phenylalanine for Y abolishes G DNA damage checkpoint control. Genetic screens in ssion yeast have identied many genes required for G checkpoint control, and like the core cell cycle regulators, these too appear to be highly conserved in evolution. The challenge with a large collection of genes is to build a model in which a rational series J.However, several observations point towards other or additional mechanisms controlling G DNA damage checkpoint arrest.Deletion of mik alone has no functional consequences, but is synthetically lethal with inactivation of wee. However, several observations in ssion yeast indicate that this model is incomplete.In ssion yeast, cells deleted for cdc compensating wee mutations either are included, which restores the balance over Y phosphorylation.Two studies have looked at the checkpoint response in these strains, but unfortunately have come to opposing conclusions.As ssion yeast is providing a key model for higher eukaryotes in dening checkpoint arrest mechanisms, these discrepancies must clearly be resolved.With the high degree of conservation of GM cell cycle and checkpoint controls, this model may indeed be generally applicable to all eukaryotes.Standard procedures and media were used for propagation and genetic manipulations supplemented with the appropriate amino acids.For cdcwee double mutants, strains were made by tetrad dissection and double mutants from nonparental ditypes were selected for immediate analysis.Filters were then placed back into the same, prewarmed and conditioned medium.