Reversible lysine acetylation is involved in DNA replication initiation by regulating activities of initiator DnaA in Escherichia coli

• Published in: Scientific reports Vol. 6; no. 1; p. 30837
• Main Authors: Zhang, Qiufen, Zhou, Aiping, Li, Shuxian, Ni, Jinjing, Tao, Jing, Lu, Jie, Wan, Baoshan, Li, Shuai, Zhang, Jian, Zhao, Shimin, Zhao, Guo-Ping, Shao, Feng, Yao, Yu-Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-08-2016; Nature Publishing Group
• Subjects: 13/44; 45/15; 45/77; 631/326; 631/80/458/1275; 82/1; 82/58; 82/83; Acetylation; Acetyltransferase; Adenosine Triphosphate - metabolism; ATP; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Chromatin; Deacetylation; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Replication; DNA, Bacterial - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; E coli; Environmental changes; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Eukaryotes; Humanities and Social Sciences; Lysine; Lysine - chemistry; Lysine - metabolism; multidisciplinary; Organophosphates - metabolism; Phosphotransferases - genetics; Phosphotransferases - metabolism; Replication initiation; Replication Origin; Science; Stationary phase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30837

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.