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About the Authors:
Ting Pang
Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States of America
ORCID http://orcid.org/0000-0001-5455-8788
Xindan Wang
Roles Formal analysis, Methodology
Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States of America
Hoong Chuin Lim
Roles Formal analysis, Methodology
Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States of America
Thomas G. Bernhardt
Roles Conceptualization, Funding acquisition, Project administration, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected] (DZR); [email protected] (TGB)
Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States of America
ORCID http://orcid.org/0000-0003-3566-7756
David Z. Rudner
Roles Conceptualization, Funding acquisition, Project administration, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected] (DZR); [email protected] (TGB)
Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, United States of America
ORCID http://orcid.org/0000-0002-0236-7143Abstract
Successive division events in the spherically shaped bacterium Staphylococcus aureus are oriented in three alternating perpendicular planes. The mechanisms that underlie this relatively unique pattern of division and coordinate it with chromosome segregation remain largely unknown. Thus far, the only known spatial regulator of division in this organism is the nucleoid occlusion protein Noc that inhibits assembly of the cytokinetic ring over the chromosome. However, Noc is not essential in S. aureus, indicating that additional regulators are likely to exist. To search for these factors, we screened for mutants that are synthetic lethal with Noc inactivation. Our characterization of these mutants led to the discovery that S. aureus Noc also controls the initiation of DNA replication. We show that cells lacking Noc over-initiate and mutations in the initiator gene dnaA suppress this defect. Importantly, these dnaA mutations also partially suppress the division problems associated with [delta]noc. Reciprocally, we show that over-expression of DnaA enhances the over-initiation and cell division phenotypes of the [delta]noc mutant. Thus, a single factor both blocks cell division over chromosomes and helps to ensure that new rounds of DNA replication are not initiated prematurely. This degree of economy in coordinating key cell biological processes has not been observed in rod-shaped bacteria and may...