The formation of FtsZ rings (Z rings) in various fts mutants was examined by immunoelectron microscopy and immunofluorescence. In two temperature-sensitive ftsZ mutants which form filaments with smooth morphology, the Z ring was unable to form. In ftsA, ftsI, and ftsQ mutants, which form filaments with an indented morphology, Z rings formed but their contraction was blocked. These results indicate that fully functional ftsA, ftsQ, and ftsI genes are not required for Z-ring formation and are unlikely to have a role in localization of the Z ring. The results also suggest that one function of the Z ring is to localize the activity of other fts gene products.It has been demonstrated by immunoelectron microscopy that FtsZ undergoes dynamic localization during the cell division cycle in both Escherichia coli and Bacillus subtilis (2,29). In these organisms, FtsZ migrates from the cytoplasm to midcell, where it is localized in a ring pattern designated the FtsZ ring (Z ring). It appears that once the Z ring is formed, septation ensues, with the Z ring maintaining a position at the leading tip of the invaginating septum. Upon completion of the septum, FtsZ disassembles and is not associated with the nascent cell pole. It has been hypothesized that the Z ring functions as a cytoskeletal element that mediates invagination of the septum (20). In vitro evidence demonstrating that FtsZ is a GTPase (12,22,25,29) and can under go GTP-dependent assembly into filaments is also consistent with this hypothesis (7,14,23). Also consistent with this hypothesis is our finding that Z rings with abnormal geometries are formed in an ftsZ26(Ts) mutant (3). Such abnormal Z rings are associated with abnormal septal morphologies, suggesting that the pattern of septal ingrowth is dictated by the shape of the Z ring.In addition to ftsZ, a number of additional genes have been identified that are required for cell division. Among the best characterized are ftsA, ftsQ, and ftsI. ftsI encodes PBP3, which is specifically required for septal peptidoglycan biosynthesis (6, 26). Presumably, this enzyme is locally activated during septation. ftsA encodes a protein that has homology to the DnaKactin family of ATPases (5). Little is known about the function of FtsQ (8).The order in which the various genes function during cell division is suggested by the morphology of the filaments produced as a result of loss of the gene function (27). A temperature-sensitive mutation in ftsZ produces filaments with a smooth morphology, whereas mutations in ftsA and ftsI produce filaments with indented morphology. These indentations are thought to arise from abortive septation events, indicating that ftsA and ftsI act after ftsZ. This order of action of these genes agrees with the order that has been inferred from the terminal phenotype observed after combining a temperaturesensitive division mutation with a mutation in the peptidoglycan elongation system which causes E. coli to grow as spheres (1). The addition of such a spherical mutation amplifies the effect of septa...

Bacterial cell division occurs through the formation of an FtsZ ring (Z ring) at the site of division. The ring is composed of the tubulin-like FtsZ protein that has GTPase activity and the ability to polymerize in vitro. The Z ring is thought to function in vivo as a cytoskeletal element that is analogous to the contractile ring in many eukaryotic cells. Evidence suggests that the Z ring is utilized by all prokaryotic organisms for division and may also be used by some eukaryotic organelles. This review summarizes our present knowledge about the formation, function, and evolution of the Z ring in prokaryotic cell division.

To better understand telomere biology in budding yeast, we have performed systematic suppressor/enhancer analyses on yeast strains containing a point mutation in the essential telomere capping gene CDC13 (cdc13-1) or containing a null mutation in the DNA damage response and telomere capping gene YKU70 (yku70Δ). We performed Quantitative Fitness Analysis (QFA) on thousands of yeast strains containing mutations affecting telomere-capping proteins in combination with a library of systematic gene deletion mutations. To perform QFA, we typically inoculate 384 separate cultures onto solid agar plates and monitor growth of each culture by photography over time. The data are fitted to a logistic population growth model; and growth parameters, such as maximum growth rate and maximum doubling potential, are deduced. QFA reveals that as many as 5% of systematic gene deletions, affecting numerous functional classes, strongly interact with telomere capping defects. We show that, while Cdc13 and Yku70 perform complementary roles in telomere capping, their genetic interaction profiles differ significantly. At least 19 different classes of functionally or physically related proteins can be identified as interacting with cdc13-1, yku70Δ, or both. Each specific genetic interaction informs the roles of individual gene products in telomere biology. One striking example is with genes of the nonsense-mediated RNA decay (NMD) pathway which, when disabled, suppress the conditional cdc13-1 mutation but enhance the null yku70Δ mutation. We show that the suppressing/enhancing role of the NMD pathway at uncapped telomeres is mediated through the levels of Stn1, an essential telomere capping protein, which interacts with Cdc13 and recruitment of telomerase to telomeres. We show that increased Stn1 levels affect growth of cells with telomere capping defects due to cdc13-1 and yku70Δ. QFA is a sensitive, high-throughput method that will also be useful to understand other aspects of microbial cell biology.

The FtsZ protein is a polymer-forming GTPase which drives bacterial cell division and is structurally and functionally related to eukaryotic tubulins. We have searched for FtsZ-related sequences in all freely accessible databases, then used strict criteria based on the tertiary structure of FtsZ and its well-characterized in vitro and in vivo properties to determine which sequences represent genuine homologues of FtsZ. We have identified 225 full-length FtsZ homologues, which we have used to document, phylum by phylum, the primary sequence characteristics of FtsZ homologues from the Bacteria, Archaea, and Eukaryota. We provide evidence for at least five independent ftsZ gene-duplication events in the bacterial kingdom and suggest the existence of three ancestoral euryarchaeal FtsZ paralogues. In addition, we identify "FtsZ-like" sequences from Bacteria and Archaea that, while showing significant sequence similarity to FtsZs, are unlikely to bind and hydrolyze GTP.