title: AdpA, key regulator for morphological differentiation regulates bacterial chromosome replication.
abstract: AdpA, one of the most pleiotropic transcription regulators in bacteria, controls expression of several dozen genes during Streptomyces differentiation. Here, we report a novel function for the AdpA protein: inhibitor of chromosome replication at the initiation stage. AdpA specifically recognizes the 5' region of the Streptomyces coelicolor replication origin (oriC). Our in vitro results show that binding of AdpA protein decreased access of initiator protein (DnaA) to the oriC region. We also found that mutation of AdpA-binding sequences increased the accessibility of oriC to DnaA, which led to more frequent replication and acceleration of Streptomyces differentiation (at the stage of aerial hyphae formation). Moreover, we also provide evidence that AdpA and DnaA proteins compete for oriC binding in an ATP-dependent manner, with low ATP levels causing preferential binding of AdpA, and high ATP levels causing dissociation of AdpA and association of DnaA. This would be consistent with a role for ATP levels in determining when aerial hyphae emerge.
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53114 Wrocław, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wolański
authors.forename: Dagmara
authors.initials: D
authors.lastname: Jakimowicz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Zakrzewska-Czerwińska
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002876:Chromosomes, Bacterial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; C114650:OriC chromosomal replication origin; D051738:Origin Recognition Complex; D015534:Trans-Activators; D000255:Adenosine Triphosphate