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A novel regulatory mechanism couples deoxyribonucleotide synthesis and DNA replication in Escherichia coli
Author(s) -
Gon Stéphanie,
Camara Johanna E,
Klungsøyr Hege K,
Crooke Elliott,
Skarstad Kirsten,
Beckwith Jon
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600990
Subject(s) - dnaa , ribonucleotide reductase , dnab helicase , biology , dna replication , origin recognition complex , pre replication complex , replication factor c , deoxyribonucleotide , prokaryotic dna replication , biochemistry , microbiology and biotechnology , origin of replication , eukaryotic dna replication , protein subunit , dna , helicase , oligonucleotide , gene , rna
We present evidence for a complex regulatory interplay between the initiation of DNA replication and deoxyribonucleotide synthesis. In Escherichia coli , the ATP‐bound DnaA protein initiates chromosomal replication. Upon loading of the β‐clamp subunit (DnaN) of the replicase, DnaA is inactivated as its intrinsic ATPase activity is stimulated by the protein Hda. The β‐subunit acts as a matchmaker between Hda and DnaA. Chain elongation of DNA requires a sufficient supply of deoxyribonucleotides (dNTPs), which are produced by ribonucleotide reductase (RNR). We present evidence suggesting that the molecular switch from ATP‐DnaA to ADP‐DnaA is a critical step coordinating DNA replication with increased deoxyribonucleotide synthesis. Characterization of dnaA and dnaN mutations that result in a constitutively high expression of RNR reveal this mechanism. We propose that the nucleotide bound state of DnaA regulates the transcription of the genes encoding ribonucleotide reductase ( nrdAB ). Accordingly, the conversion of ATP‐DnaA to ADP‐DnaA after initiation and loading of the β‐subunit DnaN would allow increased nrdAB expression, and consequently, coordinated RNR synthesis and DNA replication during the cell cycle.