Among the variety of specialized intercellular junctions, those of the adherens type have the most obvious association with cytoskeletal elements. This may be with the actin microfilanent system as in the zonula adherens or with intermediate ifiaments as in the macula adherens, or desmosome. In the former case, it is clear that transmembrane glycoproteins of the cadherin family are important adhesive components of the molecular assembly. We now show for desmosomes that a major glycoprotein component (desmosomal glycoprotein DGI) has extensive homology with the cadherins, defining an extended fmily, but also has unique features in its cytoplasmic domain that are likely to be relevant to the association with intermediate rather than actin filaments. A novel 282-residue extension contains repeats of --29 amino acid residues predicted to have an antiparallel P-sheet structure, followed by a glycine-rich sequence. As in the cadherins, the extracellular domain contains possible Ca2+-binding sequences and a potential protease processing site. The cell adhesion recognition region (His-Ala-Val) METHODSGeneration and Screening ofAntibodies. Desmosomes were isolated from bovine muzzle epidermis (4). Rabbit anti-DGI serum was generated against DGI purified by SDS/PAGE and electroelution; its specificity was similar to the guinea pig sera previously described (4). The tTo whom reprint requests should be addressed. §The sequence reported in this paper has been deposited in the GenBank data base (accession no. X56654). 4796The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

The umuDC operon of Escherichia coli encodes functions required for mutagenesis induced by radiation and a wide variety of chemicals. The closely related organism Salmonella typhimurium is markedly less mutable than E. coli, but a umu homolog has recently been identffied and cloned from the LT2 subline. In this study the nucleotide sequence and structure of the S. typhimurium LT2 umu operon have been determined and its gene products have been identified so that the molecular basis of umu activity might be understood more fully. S. typhimurium LT2 umu consists of a smaller 417-base-pair (bp) umuD gene ending 2 bp upstream of a larger 1,266-bp umuC gene. The only apparent structural difference between the two operons is the lack of gene overlap. An SOS box identical to that found in E. coil is present in the promoter region upstream of umuD. The calculated molecular masses of the umuD and umuC gene products were 15.3 and 47.8 kilodaltons, respectively, which agree with figures determined by transpositional disruption and maxicell analysis. The S. typhimurium and E. coli umuD sequences were 68% homologous and encoded products with 71% amino acid identity; the umuC sequences were 71% homologous and encoded products with 83% amino acid identity. Furthermore, the potential UmuD cleavage site and associated catalytic sites could be identified. Thus the very different mutagenic responses of S. typhimurium LT2 and E. coli cannot be accounted for by gross differences in operon structure or gene products. Rather, the ability of the cloned S. typhimurium umuD gene to give stronger complementation of E. coli umuD77 mutants in the absence of a functional umuC gene suggests that Salmonella UmuC protein normally constrains UmuD protein activity.Activity of the umuDC operon of Escherichia coli is essential for mutagenesis induced by a variety of physical and chemical agents (38,52,55). The two umu genes encode an uncharacterized activity which increases the ability of the cell to tolerate and repair damage at the expense of genetic fidelity (8,15,47). It is an interesting evolutionary feature of umu genes that analogous operons exist on many conjugative plasmids (10,22,23,32,39,48,50). Two such operons, mucAB and impCAB, have been cloned from plasmids pKM101 and TP110, respectively (10, 31).Expression of umuDC, mucAB, and impCAB genes is under the control of the SOS response (1, 6-8, 41). Under normal cellular conditions, transcription of these genes is repressed by the presence of LexA protein bound to a consensus binding sequence in the operator region of each operon (52). When DNA damage occurs, LexA repressor undergoes autoproteolytic cleavage by interaction with a complex of RecA protein, single-stranded DNA, and ATP (17, 43), and transcription of SOS-inducible genes ensues. However, for full mutagenic repair activity, the UmuD protein of E. coli or the MucA protein must itself be cleaved by interaction with the same "activated" RecA protein complex (3,9,21,25,40). The autoproteolytic cleavage of LexA, UmuD, and MucA protei...

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