title: Beyond DnaA: the role of DNA topology and DNA methylation in bacterial replication initiation.
abstract: The replication of chromosomal DNA is a fundamental event in the life cycle of every cell. The first step of replication, initiation, is controlled by multiple factors to ensure only one round of replication per cell cycle. The process of initiation has been described most thoroughly for bacteria, especially Escherichia coli, and involves many regulatory proteins that vary considerably between different species. These proteins control the activity of the two key players of initiation in bacteria: the initiator protein DnaA and the origin of chromosome replication (oriC). Factors involved in the control of the availability, activity, or oligomerization of DnaA during initiation are generally regarded as the most important and thus have been thoroughly characterized. Other aspects of the initiation process, such as origin accessibility and susceptibility to unwinding, have been less explored. However, recent findings indicate that these factors have a significant role. This review focuses on DNA topology, conformation, and methylation as important factors that regulate the initiation process in bacteria. We present a comprehensive summary of the factors involved in the modulation of DNA topology, both locally at oriC and more globally at the level of the entire chromosome. We show clearly that the conformation of oriC dynamically changes, and control of this conformation constitutes another, important factor in the regulation of bacterial replication initiation. Furthermore, the process of initiation appears to be associated with the dynamics of the entire chromosome and this association is an important but largely unexplored phenomenon.
authors.affiliation: Institute of Immunology and Experimental Therapy, Department of Microbiology, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland. Electronic address: rafal.donczew@iitd.pan.wroc.pl.
authors.forename: Rafał
authors.initials: R
authors.lastname: Donczew
authors.affiliation: Institute of Immunology and Experimental Therapy, Department of Microbiology, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland; Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-138 Wrocław, Poland. Electronic address: jolanta.zakrzewska@uni.wroc.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Zakrzewska-Czerwińska
authors.affiliation: Institute of Immunology and Experimental Therapy, Department of Microbiology, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland. Electronic address: zawilak@iitd.pan.wroc.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Zawilak-Pawlik
mesh_terms: D001419:Bacteria / Q000235:genetics*; D001426:Bacterial Proteins / Q000378:metabolism*; D019175:DNA Methylation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D051738:Origin Recognition Complex / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; C114650:OriC chromosomal replication origin; D051738:Origin Recognition Complex
keywords: DNA replication; DNA tertiary structure; nucleoid-associated proteins; oriC methylation; orisome formation