Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.

The SOS response in bacteria includes a global transcriptional response to DNA damage. DNA damage is sensed by the highly conserved recombination protein RecA, which facilitates inactivation of the transcriptional repressor LexA. Inactivation of LexA causes induction (derepression) of genes of the LexA regulon, many of which are involved in DNA repair and survival after DNA damage. To identify potential RecA-LexAregulated genes in Bacillus subtilis, we searched the genome for putative LexA binding sites within 300 bp upstream of the start codons of all annotated open reading frames. We found 62 genes that could be regulated by putative LexA binding sites. Using mobility shift assays, we found that LexA binds specifically to DNA in the regulatory regions of 54 of these genes, which are organized in 34 putative operons. Using DNA microarray analyses, we found that 33 of the genes with LexA binding sites exhibit RecA-dependent induction by both mitomycin C and UV radiation. Among these 33 SOS genes, there are 22 distinct LexA binding sites preceding 18 putative operons. Alignment of the distinct LexA binding sites reveals an expanded consensus sequence for the B. subtilis operator: 5-CGAACATATGTTCG-3. Although the number of genes controlled by RecA and LexA in B. subtilis is similar to that of Escherichia coli, only eight B. subtilis RecA-dependent SOS genes have homologous counterparts in E. coli.Exposure of prokaryotes to DNA-damaging agents results in the induction of a diverse set of physiological responses collectively called the SOS response (8, 55). As first characterized in Escherichia coli, the SOS response includes an enhanced capacity for recombinational repair, enhanced capacity for excision repair, enhanced mutagenesis (due to error-prone repair), and inhibition of cell division (i.e., filamentation). Induction of the SOS response is due to the coordinate derepression of a number of SOS or din (for damage-inducible) genes. The SOS response to DNA damage in Bacillus subtilis is similar to that of E. coli (26,56,58), but unlike E. coli, the B. subtilis SOS system is also induced in competent cells in the absence of any DNA-damaging treatment (25, 57, 58). As in E. coli, SOS gene expression in B. subtilis is controlled by two proteins (which are themselves products of SOS genes): the LexA protein (also called DinR) (40,54), which represses the transcription of din genes by binding to the SOS operator (31), and the RecA protein (30), which is activated by single-stranded DNA (29,42) to stimulate the proteolytic autodigestion of LexA (24,31). Thus, an SOS gene is defined by two criteria-RecA-dependent induction by DNA damage and a binding site for LexA overlapping its promoter.By contrast with E. coli, where more than 30 SOS genes have been identified (7,8), only 5 B. subtilis SOS genes have been shown to meet both SOS gene criteria thus far: recA, lexA, uvrB (formerly dinA), dinB, and dinC (also called tagC) (4,9,15,25).