Figure 1.
DSB Repair by the NHEJ Complex
The Ku complex locates to the break site (step 1), where it may serve as an end-bridging and alignment factor. Following binding to the broken DNA ends, additional processing enzymes are recruited by Ku to the break site (step 2). Ku may translocate away from the ends, allowing access by other factors to the break termini. When DNA ends are non-complementary and/or are damaged, the DNA end-processing, gap-filling, and nucleolytic activities generate DNA termini, capable of being ligated, prior to ligation (step 3). Subsequently, the broken ends are joined by an NHEJ-specific DNA ligase (step 4) and the NHEJ complex dissociates.
Figure 2.
Phylogenetic Distribution of the NHEJ Ku Protein in Bacteria
A diagrammatic tree representation of major phyla, classes, and families of bacteria, as indicated by the relevant names is shown. Lines between the names illustrate well-established phylogenetic links within the various phyla. Stars in green indicate phyla that contain homologues of Ku. Numbers in green indicate the number of species with completed genome sequences that are within each phylum and contain one (or more) homologue(s) of Ku. Stars in blue indicate classes/orders that contain homologues of Ku. Numbers in blue indicate the number of species with completed genome sequences that are within each class that contain one (or more) homologue(s) of Ku. Stars in red indicate families that contain homologues of Ku. Note that there is no instance in which a Ku homologue is contained in all species within a phylum/class.
Figure 3.
Structure of Eukaryotic, Prokaryotic, and Phage Ku Proteins
The structure of the human Ku heterodimer bound to DNA [22] is depicted in two different orientations. Ku encircles the end of the DNA like a “nut on a bolt.” The predicted structures of the Ku from Mt and Gam homodimers are also shown. The smaller Ku homologues retain the regions required for dimerization and DNA binding but lack the N-terminal vWA domains, the C-terminal SAP (Ku70), and the DNA-PKcs binding (Ku80) domains present in the larger eukaryotic Ku proteins.
Figure 4.
Domain Organization of Prokaryotic NHEJ Repair Enzymes
Prokaryotic NHEJ DNA ligases exhibit a variety of arrangements of catalytic domains. Representative examples are presented showing the approximate location of the individual domains (amino acid): from Mt, Mt-LigD (polymerase, 1–280; nuclease, 281–460; ligase, 461–760); from P. aeruginosa, PA2138 (nuclease, 1–200; ligase, 201–550; polymerase, 551–841); and from B. subtilis, YkoU (ligase, 1–320; polymerase, 321–611). Putative “stand-alone” NHEJ proteins containing related DNA ligase, polymerase, and nuclease domains are also included—SCO refers to S. coelicolor and AF refers to A. fulgidus.