Alternative splicing is an important source of protein diversity, and is an 
established but not yet fully understood mechanism for gene regulation in higher 
eukaryotes. Its regulation is governed by a variety of mechanisms, including 
variation in the expression levels of splicing factors engaged in spliceosome 
formation. SRp55 is one of the most ubiquitous splicing factors and one that can 
be up-regulated by DNA damage in the absence of p53, and we had previously found 
that depletion of its activity increased resistance to DNA damage in 
p53-dependant manner. To assess its influence on the splicing patterns of genes 
involved in apoptosis, we performed splice-specific microarray analysis of cells 
treated with siRNA specific for this gene. This analysis, backed by RT-PCR 
verification, identified three genes, KSR1, ZAK and mda7/IL24, which are 
sensitive to SRp55 depletion. We also analyzed the splice patterns of 
apoptosis-related genes in p53-deficient U2OS cells following treatment with the 
genotoxic drug mitomycin C. This analysis revealed that DNA damage resulted in 
changes in splicing activity that modified the splicing pattern of Fas, a key 
pro-apoptotic, p53-inducible death receptor. Interestingly, this modification 
led to an enrichment of the anti-apoptotic soluble Fas isoform, and this 
secreted isoform was detected in the media surrounding cells subjected to DNA 
damage. These findings show that modulation of splicing activity in 
p53-deficient cells during the early response to sub-lethal DNA damage results 
in a change in the splicing of target genes, thus modifying the cellular 
response to genotoxic agents.