title: Reversible lysine acetylation is involved in DNA replication initiation by regulating activities of initiator DnaA in Escherichia coli.
abstract: The regulation of chromosomal replication is critical and the activation of DnaA by ATP binding is a key step in replication initiation. However, it remains unclear whether and how the process of ATP-binding to DnaA is regulated. Here, we show that DnaA can be acetylated, and its acetylation level varies with cell growth and correlates with DNA replication initiation frequencies in E. coli. Specifically, the conserved K178 in Walker A motif of DnaA can be acetylated and its acetylation level reaches the summit at the stationary phase, which prevents DnaA from binding to ATP or oriC and leads to inhibition of DNA replication initiation. The deacetylation process of DnaA is catalyzed by deacetylase CobB. The acetylation process of DnaA is mediated by acetyltransferase YfiQ, and nonenzymatically by acetyl-phosphate. These findings suggest that the reversible acetylation of DnaA ensures cells to respond promptly to environmental changes. Since Walker A motif is universally distributed across organisms, acetylation of Walker A motif may present a novel regulatory mechanism conserved from bacteria to eukaryotes.
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Qiufen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Li
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Ni
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Wan
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Lab of Genetic Engineering &Institutes of Biomedical Sciences, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhao
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
authors.affiliation: Laboratory of Bacterial Pathogenesis, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yao
mesh_terms: D000107:Acetylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D010755:Organophosphates / Q000378:metabolism*; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D018741:Replication Origin
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C066312:DnaA protein, Bacteria; D029968:Escherichia coli Proteins; D010755:Organophosphates; C011632:acetyl phosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C434675:NadK protein, E coli; D008239:Lysine