e, A3A, is in principle capable of explaining the four hallmarks of cancer genomes -i) huge numbers of mutations, ii) most of which are CG->TA and CG->NN, iii) 5MeCpG hotspots and iv) double strand DNA breaks. Clearly human A3A can be a danger to cellular genomic integrity. The A3A precursor has been traced back some 140 13 APOBEC3A Isoforms Induce DNA Damage and Apoptosis Myr and cuts across the primate, carnivore and artiodactyl orders suggesting that the physiological role of the A3A enzyme has been well honed. To date no human A3A-/genotype has been described. The contrast between AID and A3A is striking, the more so as the A3 locus presumably arose by duplication of the older AID gene. AID enzyme has lower catalytic activity and is targeted to discrete loci in B cells, the DNA breaks made being 11303052 rapidly repaired with off target deamination is something of a rarity. It appears that A3A has undergone selection for extremely efficient non-targeted cytidine deamination of nuDNA. Local A3A induced mutation rates that can reach something between 0.1 and 0.8 per base, which is more than enough to push the cell beyond the error threshold, a well known concept to RNA virologists, into some form of caspase-3 independent cell death. Recently, we described TRIB3 as a pseudokinase that degrades A3A so protecting the genome. Intriguingly it is part of the CtIP-Rb-BRCA1-ATM protein 9435190 network. It is remarkable that such opposites, genome stability and A3A hypermutagenesis, are part of the same network, as though the latter might possibly be a mechanism of last resort in the case of genetic conflicts. The hypermutated nuDNA and DSBs identified in INF- treated CD4+ T lymphocytes suggests that A3A induced DNA damage is far from a rare phenomenon. The pathological consequences of dysfunctional A3A gene control need to be explored especially as many cancers emerge in a background of chronic inflammation. Acknowledgements We would like to thank Helen Law and Milena Hasan for their excellent help with the ImageStream technology. In vertebrates many inner organs of the chest and abdomen, such as heart and stomach, are asymmetrically localized along the left-right body axis. Initiation of LR asymmetry in fish, amphibians and mammals is achieved by a cilia-driven leftward flow of extracellular fluids during neurulation. Ciliated epithelia exist only very transiently and are represented by the amphibian GRP, Kupffer’s vesicle in fish and posterior notochord in mammals. The lateral margins of these epithelia are characterized by cells which co-express the growth factor nodal as well as a nodal inhibitor . As a result of asymmetric flow, the expression of the nodal inhibitor on the left side is down-regulated, which is thought to order HC-030031 release nodal repression and initiate the nodalcascade exclusively in the left lateral plate mesoderm. Wnt signaling is a highly complex and multiple branched signaling pathway, which plays a plethora of important roles during animal development, tissue homeostasis and in human disease. During LR axis development the canonical Wnt/ b-catenin pathway initiates the expression of the transcription factor Foxj1, a master regulator of motile cilia, in the SM. The SM represents a part of the epithelial outer layer of the gastrula embryo. It neighbors the organizer caudally and involutes during gastrulation to give rise to the GRP. Foxj1 expression in Kupffer’s vesicle of zebrafish embryos is also regulated by Wnt/ b-catenin, indicating conse