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Alan D. Grossman. Anderson, Mary E.,Ph. D.(Mary Elizabeth)Massachusetts Institute of Technology. Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology 2019-07-22T19:32:51Z 2019-07-22T19:32:51Z 2019 https://hdl.handle.net/1721.1/121876 1102636605 Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019 Cataloged from PDF version of thesis. "February 2019." Includes bibliographical references (pages 118-128). DNA replication is a highly regulated process across all organisms. Improper regulation of DNA replication can be detrimental. I identified an overinitiating, conditional synthetic lethal mutant of Bacillus subtilis. I isolated suppressors of this mutant and uncovered novel genes associated with DNA replication. These suppressors acted both at the steps of initiation and elongation to overcome the detrimental replication initiation of the synthetic lethal [delta]yabA dnaA 1 mutant. One class of suppressors decreased levels of the replicative helicase, DnaC. I showed that decreased levels of helicase are sufficient to limit replication initiation under fast growth conditions. I also explored the regulation of DnaA as a transcription factor. The replication initiation inhibitor, YabA, binds to DnaA and prevents its cooperative binding at the origin. In addition to its role in replication initiation, DnaA also directly regulates expression of several genes. YabA has been shown to inhibit DnaA binding at several promoters but its effect on DnaA-mediated gene expression is unclear. I found that YabA inhibits sda activation by DnaA but does not significantly affect repression of ywlC by DnaA. Lastly, I showed that YabA appears to stimulate autoregulation of dnaA. This preliminary data illustrates a role for YabA regulation in DnaA-mediated gene expression. by Mary E. Anderson. Ph.D. Ph.D. Massachusetts Institute of Technology, Department of Biology 128 pages eng Massachusetts Institute of Technology MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. Regulation of DNA replication and the replication initiator, DnaA, in Bacillus subtilis Thesis application/pdf 2019-07-22T19:32:44Z Publication Doctoral Bio unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4e6ac5e6-1aa3-49d4-a5c6-0bde60d03b4d"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Regulation of DNA replication and the replication initiator, DnaA, in Bacillus subtilis</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2019</PublicationDate> <Authors> <Author> <DisplayName>Anderson, Mary E.,Ph. D.(Mary Elizabeth)Massachusetts Institute of Technology.</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>DNA replication is a highly regulated process across all organisms. Improper regulation of DNA replication can be detrimental. I identified an overinitiating, conditional synthetic lethal mutant of Bacillus subtilis. I isolated suppressors of this mutant and uncovered novel genes associated with DNA replication. These suppressors acted both at the steps of initiation and elongation to overcome the detrimental replication initiation of the synthetic lethal [delta]yabA dnaA 1 mutant. One class of suppressors decreased levels of the replicative helicase, DnaC. I showed that decreased levels of helicase are sufficient to limit replication initiation under fast growth conditions. I also explored the regulation of DnaA as a transcription factor. The replication initiation inhibitor, YabA, binds to DnaA and prevents its cooperative binding at the origin. In addition to its role in replication initiation, DnaA also directly regulates expression of several genes. YabA has been shown to inhibit DnaA binding at several promoters but its effect on DnaA-mediated gene expression is unclear. I found that YabA inhibits sda activation by DnaA but does not significantly affect repression of ywlC by DnaA. Lastly, I showed that YabA appears to stimulate autoregulation of dnaA. This preliminary data illustrates a role for YabA regulation in DnaA-mediated gene expression.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>