Negative control of DNA replication by hydrolysis of ATP bound to DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli

Mizushima, Tohru; Nishida, Satoshi; Kurokawa, Kenji; Katayama, Tsutomu; Miki, Takeyoshi; Sekimizu, Kazuhisa

doi:10.1093/emboj/16.12.3724

Cited by 63 publications

(83 citation statements)

References 31 publications

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“…In Escherichia coli, considered as a paradigm for initiation studies in eubacteria, the regulatory inactivation of DnaA (RIDA) acts after initiation to promote the switch from the active ATP-DnaA to the inactive ADP-DnaA form. RIDA is mediated by the Hda protein and requires the slidingclamp DnaN (2)(3)(4)(5). A second level of regulation is mediated by the sequestration of the oriC region by the SeqA protein, which binds with a high affinity to hemimethylated GATC sequences within oriC, thus temporarily restraining reintitiation (6)(7)(8).…”

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confidence: 99%

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Noirot‐Gros

Velten

Yoshimura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

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The regulation of initiation of DNA replication is crucial to ensure that the genome is replicated only once per cell cycle. In the Gram-positive bacterium Bacillus subtilis, the function of the YabA protein in initiation control was assigned based on its interaction with the DnaA initiator and the DnaN sliding clamp in the yeast two-hybrid and on the overinitiation phenotype observed in a yabA null strain. However, YabA is unrelated to known regulators of initiation and interacts with several additional proteins that could also be involved directly or not in initiation control. Here, we investigated the specific role of YabA interactions with DnaA and DnaN in initiation control by identifying single amino acid changes in YabA that disrupted solely the interaction with DnaA or DnaN. These disruptive mutations delineated specific interacting surfaces involving a Zn 2؉ -cluster structure in YabA. In B. subtilis, these YabA interaction mutations abolished both initiation control and the formation of YabA foci at the replication factory. Upon coexpression of deficient YabA mutants, mixed oligomers formed foci at the replisome and restored initiation control, indicating that YabA acts within a heterocomplex with DnaA and DnaN. In agreement, purified YabA oligomerized and formed complexes with DnaA and DnaN. These findings underscore the functional association of YabA with the replication machinery, indicating that YabA regulates initiation through coupling with the elongation of replication.DnaA ͉ DnaN ͉ Gram-positive bacteria ͉ initiation control

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mentioning

confidence: 99%

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Noirot‐Gros

Velten

Yoshimura

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

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“…DnaA has intrinsic ATPase activity, and ATP bound to DnaA can be hydrolyzed to ADP (1). This hydrolysis inactivates the ATPDnaA complex into the ADP-DnaA complex and suppresses re-replication; in other words, it suppresses over-initiation of DNA replication (4,5). Acidic phospholipids, such as cardiolipin, interact with the conserved basic amino acid residues of DnaA and stimulate the release of ADP from the ADP-DnaA complex, resulting in re-activation (6 -9).…”

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confidence: 99%

Kinetics of ATP Binding to the Origin Recognition Complex of Saccharomyces cerevisiae

Makise

Takenaka

Kuwae

et al. 2003

Journal of Biological Chemistry

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Origin recognition complex (ORC), a candidate initiator of chromosomal DNA replication in eukaryotes, binds specifically to ATP through two of its subunits (Orc1p and Orc5p). In this study, we investigated the kinetics of ATP binding to ORC by a filter binding assay. The K d values for the ATP of wild-type ORC and ORC-1A (mutant ORC containing Orc1p with a defective Walker A motif) were less than 10 nM, suggesting that the affinity of Orc5p for ATP is very high. On the other hand, the K d values for the ATP of ORC-5A (mutant ORC containing Orc5p with a defective Walker A motif) was much higher (about 1.5 M), suggesting that the affinity of Orc1p for ATP is relatively low in the absence of origin DNA. ATP dissociated more rapidly from its complex with ORC-5A than from its complex with ORC-1A, suggesting that the ATP-Orc5p complex is more stable than ATP-Orc1p complex. Origin DNA fragments decreased the K d value of ORC-5A for ATP and stabilized the complex of ATP with ORC-5A. Wild-type ORC, ORC-1A, and ORC-5A required different concentrations of ATP for specific binding to origin DNA. All of these results imply that ATP binding to Orc5p, ATP binding to Orc1p, and origin DNA binding to ORC are co-operatively regulated, which may be important for the initiation of DNA replication.

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“…DnaA219 (A184V, H252Y and R342C) was found to be a lethal over-initiation phenotype, as was the case for DnaAcos [31,33]. This phenotype can be explained by the fact that they are active without binding to ATP [31,33], because ATP hydrolysis is involved in DnaA inactivation to suppress the over-initiation [34,35]. However, DnaA435 was not a lethal over-initiation phenotype (Table 1), although this protein was active without binding to ATP (Figures 3 and 6).…”

Section: Replication Activity Of Mutant Dnaa Proteins In Vitromentioning

confidence: 99%

Biochemical analysis of DnaA protein with mutations in both Arg328 and Lys372

et al. 2002

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Negative control of DNA replication by hydrolysis of ATP bound to DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli

Abstract: reported that synthesized organic compounds which were Japan designed to block the ATP binding to DnaA protein specifically inhibited the oriC DNA replication in vitro 1 Corresponding author e-mail: sekimizu@bisei.phar.kyushu-u.ac.jp (Mizushima et al., 1996c

Cited by 63 publications

References 31 publications

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis

Kinetics of ATP Binding to the Origin Recognition Complex of Saccharomyces cerevisiae

Biochemical analysis of DnaA protein with mutations in both Arg328 and Lys372

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