title: Replication fork passage drives asymmetric dynamics of a critical nucleoid-associated protein in Caulobacter.
abstract: In bacteria, chromosome dynamics and gene expression are modulated by nucleoid-associated proteins (NAPs), but little is known about how NAP activity is coupled to cell cycle progression. Using genomic techniques, quantitative cell imaging, and mathematical modeling, our study in Caulobacter crescentus identifies a novel NAP (GapR) whose activity over the cell cycle is shaped by DNA replication. GapR activity is critical for cellular function, as loss of GapR causes severe, pleiotropic defects in growth, cell division, DNA replication, and chromosome segregation. GapR also affects global gene expression with a chromosomal bias from origin to terminus, which is associated with a similar general bias in GapR binding activity along the chromosome. Strikingly, this asymmetric localization cannot be explained by the distribution of GapR binding sites on the chromosome. Instead, we present a mechanistic model in which the spatiotemporal dynamics of GapR are primarily driven by the progression of the replication forks. This model represents a simple mechanism of cell cycle regulation, in which DNA-binding activity is intimately linked to the action of DNA replication.
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Arias-Cartin
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA.|Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
authors.forename: Genevieve S
authors.initials: GS
authors.lastname: Dobihal
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.|Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Campos
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.|Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Surovtsev
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Parry
authors.affiliation: Microbial Sciences Institute, Yale University, West Haven, CT, USA christine.jacobs-wagner@yale.edu.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.|Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.|Department of Microbial Pathogenesis, Yale Medical School, Yale University, New Haven, CT, USA.
authors.forename: Christine
authors.identifier: 0000-0003-0980-5334
authors.initials: C
authors.lastname: Jacobs-Wagner
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle; D004261:DNA Replication; D015964:Gene Expression Regulation, Bacterial; D023281:Genomics; D008962:Models, Theoretical; D061848:Optical Imaging; D011485:Protein Binding; D062211:Spatio-Temporal Analysis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors
keywords: 
  Caulobacter
  ; DNA replication; cell cycle; chromosome organization; nucleoid‐associated protein