Diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) controls the timing of cell division in Escherichia coli.
BACKGROUND
The timing of the cell division in Escherichia coli is highly regulated, but its mechanism has not been identified. Previously we have found that the cfcA1 mutation uncouples DNA replication and cell division and elevates the frequency of cell division. We further analysed the structure and the role of the cfc genes of cfcA11, a derivative of cfcA1, and another cfc mutant, cfcB1.


RESULTS
The cfc mutants divided prior to the ordinary stage of cell division and produced many small cells with nucleoid. However, the cells grew exponentially, and the length of a cell cycle and the initiation mass for chromosome replication were not altered by the cfc mutations. These properties resulted from a reduction of the period between the nucleoid division and the cell division in a cell cycle, and a compensatory lengthening of the period between the cell division and the initiation of the next round of DNA replication. CfcA11 has a mutation in glySa which encodes the alpha-subunit of glycyl-tRNA synthetase, and cfcB1 has an IS2 insertion in apaH which encodes Ap4A hydrolase. The cfc properties of both cfc mutants were suppressed by a multicopy plasmid carrying apaH+, and the intracellular level of Ap4A in cfcA1 was 15-fold higher, and cfcB1 was 100-fold higher than their parent. Experiments using wild-type cells showed that a high level of Ap4A caused early cell division, and that a low level of Ap4A caused delayed cell division.


CONCLUSIONS
Ap4A is a signal for the induction of cell division. High levels of Ap4A are responsible for the initiation of cell division. The glyS mutation permits an efficient synthesis of Ap4A.
Nishimura
A
A
National Institute of Genetics, Mishima, Japan. anishimu@lab.nig.ac.jp
Moriya
S
S
Ukai
H
H
Nagai
K
K
Wachi
M
M
Yamada
Y
Y
D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D004261:DNA Replication; D004269:DNA, Bacterial / Q000096:biosynthesis; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics*; D005798:Genes, Bacterial; D006032:Glycine-tRNA Ligase / Q000235:genetics; D009154:Mutation
D004269:DNA, Bacterial; D015226:Dinucleoside Phosphates; C020733:diadenosine tetraphosphate; D006032:Glycine-tRNA Ligase