Cell division is essential for living organisms. Prokaryotic and eukaryotic mechanisms precisely coordinate division so that it happens only when DNA replication is complete. The work presented in this thesis explores how ObgE, an essential GTPase in Escherichia coli , coordinates cell division with DNA replication. This crucial coordination prevents premature division and cell death. To identify this mechanism, we explored how obgE mutants respond to treatment with replication inhibitors and DNA damaging agents. Expression of a C-terminus and a GTP-locked mutant prevented proper cell division after treatment with DNA replication inhibitors and DNA damaging agents. This inhibition was enhanced when cells lost their capability to induce the SOS response, a DNA damage pathway. The SOS regulators, lexA and recA were needed for ObgE-dependent inhibition. Expression of SulA, the SOS division regulator, was partially required for inhibition. We propose that an ObgE-dependent pathway requires DNA damage for induction and in part, lexA,recA and sulA,. The cytokinetic ring is essential for division. Assembly of this ring, the FtsZ-ring requires two proteins, FtsA and ZipA in Escherichia coli. We explore the link between ObgE, FtsA and ZipA. ftsA mutants bypass filamentation from ObgE depletion. Expression of the C-terminus insertion mutant, obgE::Tn5 restores the positioning of a FtsA localization mutant. This C-terminus appears to be important for division since obgE::Tn5 also restores cell division when a ZipA mislocalization mutant is expressed. Since ObgE localizes to division sites, it may function with FtsA and ZipA to mediate assembly of the FtsZ-ring. We provide a general link to our findings and propose a model wherein an ObgE and DNA damage inducible pathway operates via FtsA and ZipA assembly of the FtsZ ring.
|Advisor:||Lovett, Susan T.|
|Commitee:||Hedstrom, Lizbeth K., Walker, Graham, Yoshida, Satoshi|
|School Location:||United States -- Massachusetts|
|Source:||DAI-B 75/06(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Microbiology|
|Keywords:||Cell division, DNA replication, GTPases, ObgE|
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