Ssociated with these operons. As a result we identified two uncharacterized
Ssociated with these operons. As a result we identified two uncharacterized superfamilies that tended to strongly co-occur with the mutagenic SOS operons across most major lineages of the bacterial tree (Figure 1 and Additional file 1; 25 and 65 of all their recovered gene neighborhood showed such associations). The first of these is typified by the Bacillus subtilis YoqW protein (gi: 384175670) and the E.coli protein YedK (gi: 49176171), and contains a globular domain of about 220-260 residues in length, which was previously described as containing a domain of unknown (DUF159) in the Pfam database [16]. The second of these codes for a protein prototyped by Geobacter sulfurreducens GSU0042 (gi: 39995153) and contains a previously unknown, small, globular domain approximately 80 residues in length. Iterative sequence profile searches with PSI-BLAST and hidden Markov model searches with HMMSEARCH using an alignment of different representatives of this domain showed that it was related to a conserved domain found in the ImuB family of proteins that occurs C-terminal to the family Y DNA polymerase domain. For instance, HMMSEARCH using a HMM derived from the small GSU0042-like proteins recovered the ImuB C-terminal domains with e-value 10-4-10-5. Likewise, a search initiated using the Syntrophomonas wolfei protein Swol_1669 (gi: 114567184) recovered the ImuB C-terminal domains in a PSI-BLAST search (e-value = 10-3-10-4; iteration 7). Accordingly, we named this conserved domain the ImuB-C (for ImuB C-terminal) domain.Aravind et al. Biology Direct 2013, 8:20 http://www.biology-direct.com/content/8/1/Page 3 ofFigure 1 Operons and contextual network graph of the SRAP and ImuB-C containing proteins. Genes are represented as arrows, with the arrow head pointing from the 5′ to the 3′ direction. Operons are labeled with the gi number of the SRAP or ImuB-C gene in the neighborhood followed by the species name. Standard names of encoded domains are used to label genes, the rest being MPep, metallopeptidase; ATPDL, ATP-dependent DNA ligase. In the network graph, genes are represented as nodes, and edges indicate the gene context with the arrow head pointing to the gene in the 3′ direction of the neighborhood. Edges depicting genes arranged in diverging directions are shown with circular ends. Pfam DUF4130 is a predicted mutagenesisrelated enzyme that is associated with the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27735993 BKT140 site SplB-like radical SAM photolyases and uracil DNA glycosylases, which might modify thymines.Contextual and sequence-structure analyses reveal the DUF159 domain to be a DNA-associated autopeptidaseTo better understand the role of the DUF159 proteins in the SOS response we carefully examined their gene contexts and found that they are encoded in at least threedistinct operonic contexts related to the SOS response (Figure 1): 1) as neighbors of the UmuC-UmuD gene dyad that code for subunits of the translesion DNA PolV; 2) Alongside two or more genes that constitute the widespread mutagenic gene cluster namely ImuB, ImuA, andAravind et al. Biology Direct 2013, 8:20 http://www.biology-direct.com/content/8/1/Page 4 ofDnaE2 [1,9,10]; 3) As part of an operon with DinB (coding for translesion Pol IV). Exemplars of this geneneighborhood might further include LexA [1] or genes for bacterial versions of the DNA end-binding Ku protein and the ATP-dependent DNA ligase [17] or in certain cases a DnaE paralog. Conserved gene-neighborhoods combining the DUF159 and Ku genes also code for two previous.
