Chromosomal fragmentation in "Escherichia coli" is a lethal event for the cell unless mended by the recombinational repair proteins RecA, RecBCD, and RuvABC. Certain mutations exacerbate problems that cause the cell to be dependent on the recombinational repair proteins for viability. We tested whether the absence of the MutT protein caused replication fork collapse in recombinational repair mutants similar to known Rec-dependent mutants with analogous functions, and investigated the nature of the chromosomal fragmentation in "seqA recA" co-lethality. Nucleotide pool sanitizing enzymes Dut (dUTPase), RdgB (dITPase), and MutT (8-oxo-dGTPase) hydrolyze non-canonical DNA precursors to prevent incorporation of base analogs into DNA. Previous studies reported dramatic AT[arrow right]CG mutagenesis in "mutT" mutants, suggesting a considerable density of 8-oxo-G in DNA that should cause frequent excision and chromosomal fragmentation, irreparable in the absence of RecBCD-catalyzed repair, similar to the lethality of "dut recBC" and "rdgB recBC" double mutants. In contrast, we found "mutT recBC" double mutants viable with no signs of chromosomal fragmentation. Over-production of the MutM and MutY DNA glycosylases, both acting on DNA containing 8-oxo-G, still yields no lethality in "mutT recBC" double mutants. Plasmid DNA, extracted from "mutT mutM" double mutant cells and treated with MutM in vitro, shows no increased relaxation, indicating no additional 8-oxo-G modifications. We calculate less than four 8-oxo-Gs per genome equivalent, which is too low to cause the expected effects. We conclude that, in contrast to the previous studies, there is not enough 8-oxo-G in the DNA of "mutT" mutants to cause the elevated excision repair that would trigger chromosomal fragmentation. Based on these results, we propose that the main target of MutT in "E. coli" is "syn" -dGTP, rather than 8-oxo-dGTP. An insertion in "seqA" was isolated in a screen for mutants dependent on recombinational repair. The "seqA" defect in "E. coli" is presumed to overinitiate chromosome replication, with the resulting chromosomal fragmentation causing the "seqA recA" co-lethality. A precise deletion of "seqA" is somewhat cold-sensitive, has an elevated ratio of origin DNA to terminus DNA, suffers from chromosomal fragmentation, and is induced for the SOS response. "[delta]seqA [delta]recA", "[delta]seqA [delta]recBCD", and "[delta]seqA [delta]ruvABC" mutants have greatly reduced viability at 42[degrees Celsius] and are completely inviable at lower temperatures. To understand the nature of this chromosomal fragmentation, we characterized the "[delta]seqA" mutants and isolated suppressors of the "seqA recA" lethality. The fragmented pieces of the chromosome that result from a "seqA recBC" mutant hybridize predominantly to an origin-proximal probe, rather than a terminus proximal one, indicating that the breaks depend on replication. By tracking the level of origin and terminus DNA per cell mass over the growth of a culture, we found that "[delta]seqA" mutants are actually underreplicating the terminus, rather than overinitiating at the origin. "[delta]seqA" mutants likely suffer from replication fork stalling and subsequent breakage. The genetic approach we used included isolating suppressors of the "[delta]seqA [delta]recA" inviability at low temperatures and categorizing them by their ability to alleviate chromosomal fragmentation and reduce the on/ter ratio. Many of the strong suppressors lower the replication initiation potential by interfering with the DnaA initiator protein. Another category reduces the extra negative superhelicity of the chromosome. Approximately 70% of the insertions interfere with LPS core phosphorylation in the outer membrane ("rfaQ," "rfaG," and "rfaP" mutants). Surprisingly, the "rfa" mutants do not alleviate chromosomal fragmentation or SOS induction, although they do decrease the on/ter ratio. We tested the idea that LPS may participate in rejuvenating inactive DnaA initiator protein, much like acidic phospholipids in the inner membrane, but concluded that this was not the case. While studying "mutT" and "seqA" mutants, we discovered a contaminating bacteriophage We studied, sequenced, and identified the phage as phi80. We looked at three interesting phenotypes: modification of the phage DNA to protect against restriction enzymes, sensitivity of lysogens to UV damage, and the toxicity when the "gam" gene was overexpressed in the cell. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]