Chaperone‐mediated reduction of RepA dimerization is associated with RepA conformational change

Dibbens, Justin A.; Muraiso, Kanae; Chattoraj, Dhruba K.

doi:10.1046/j.1365-2958.1997.5691920.x

Cited by 25 publications

(29 citation statements)

References 38 publications

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“…The conformation of some ORC subunits seems to be different when the complex is assembled free or associated with autonomously replicating sequence DNA, a process in which ATP is the allosteric effector (8,34). We propose that, by analogy with DnaK effects on RepA (16,(20)(21)(22)(23), Hsp70 could also switch ScOrc4p between different functional states in the replication complex. Further experiments are required to test this hypothesis.…”

Section: Structural and Functional Similarities Between Repa And Scorc4pmentioning

confidence: 99%

“…DnaK dissociates RepA dimers into functional monomers (20)(21)(22)(23) and disassembles oligomers of DnaA into an active form (35). Hsp70, the eukaryotic homologue of DnaK, binds to the human papilloma virus initiator E1, stimulating origin recognition and replication (36).…”

Section: E Coli Dnak Chaperone Binds and Disassembles Oligomers Of Tmentioning

confidence: 99%

“…Dissociation of RepA dimers can either occur spontaneously (14,20) or be mediated by DnaK͞Hsp70 chaperones (21). Monomerization is coupled to a conformational change (22,23) in the N-terminal domain in RepA. As a result both the N-and C-terminal domains of the monomer show DNA binding, whereas in the dimer only the C-terminal domain is involved in DNA binding (16).…”

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confidence: 99%

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Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p)

Giraldo

Dı́az-Orejas

2001

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

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The proteins responsible for the initiation of DNA replication are thought to be essentially unrelated in bacteria and archaea͞ eukaryotes. Here we show that RepA, the initiator from the Pseudomonas plasmid pPS10, and the C-terminal domain of ScOrc4p, a subunit of Saccharomyces cerevisiae (Sc) origin recognition complex (ORC), share sequence similarities. Based on biochemical and spectroscopic evidence, these similarities include common structural elements, such as a winged-helix domain and a leucine-zipper dimerization motif. We have also found that ScOrc4p, as previously described for RepA-type initiators, interacts with chaperones of the Hsp70 family both in vitro and in vivo, most probably to regulate the assembly of active ORC. In evolutionary terms, our results are compatible with the recruitment of the same protein module for initiation of DNA replication by the ancestors of present-day Gram-negative bacteria plasmids, archaea, and eukaryotes.T he universality of the processes involved in the transmission of genetic information has been interpreted to reflect a common evolutionary history. Thus it is accepted that life originated from self-replicating RNA molecules capable of directing protein synthesis, to be replaced later by DNA as the genetic material (1). However, this view has been challenged by modern genomics, inasmuch as protein sequence comparisons conclude that the set of genes for replication, transcription, and translation in bacteria differs from that found in archaea and eukarya (2). Divergence is noteworthy for proteins that initiate chromosomal DNA replication in bacteria (DnaA) (3) and eukarya (the six subunits of the origin recognition complex, ORC) (4, 5); despite their common function in binding to DNA replicators, they lack significant sequence similarity, other than an AATϩ module for ATP binding (6-8). However, structural similarities have been found among some of the accessory factors of prokaryotic and eukaryotic replicative DNA polymerases (9-11).We had previously found in RepA, the Pseudomonas plasmid pPS10 DNA replication initiator protein (12), the leucine-zipper (LZ) (13, 14) and helix-turn-helix (15) sequence motifs that function in protein dimerization and protein-DNA interaction, respectively. These motifs are part of two repeated winged-helix (WH) domains (16). In common with other homologous plasmid initiators (17, 18), RepA molecules exist as monomers and dimers in equilibrium (14). The monomers activate initiation of replication by binding to directly repeated DNA sequences (14, 16), whereas the dimers repress repA transcription by binding to an inversely repeated DNA operator (19,16). Dissociation of RepA dimers can either occur spontaneously (14,20) or be mediated by DnaK͞Hsp70 chaperones (21). Monomerization is coupled to a conformational change (22,23) in the N-terminal domain in RepA. As a result both the N-and C-terminal domains of the monomer show DNA binding, whereas in the dimer only the C-terminal domain is involved in DNA binding (16). This model was recent...

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Section: Structural and Functional Similarities Between Repa And Scorc4pmentioning

confidence: 99%

Section: E Coli Dnak Chaperone Binds and Disassembles Oligomers Of Tmentioning

confidence: 99%

mentioning

confidence: 99%

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Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p)

Giraldo

Dı́az-Orejas

2001

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

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“…Dimerization is also efficient because purified RepA is predominantly dimeric, although the monomers are required for replication and autorepression (29,31). Monomerization requires remodeling primarily by chaperones DnaJ and DnaK (32,33). Only the remodeled monomers bind iterons efficiently, allowing replication and autorepression.…”

Section: Resultsmentioning

confidence: 99%

Multiple homeostatic mechanisms in the control of P1 plasmid replication

Das

Valjavec-Gratian

Basuray

et al. 2005

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

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Many organisms control initiation of DNA replication by limiting supply or activity of initiator proteins. In plasmids, such as P1, initiators are limited primarily by transcription and dimerization. However, the relevance of initiator limitation to plasmid copy number control has appeared doubtful, because initiator oversupply increases the copy number only marginally. Copy number control instead has been attributed to initiator-mediated plasmid pairing (''handcuffing''), because initiator mutations to handcuffing deficiency elevates the copy number significantly. Here, we present genetic evidence of a role for initiator limitation in plasmid copy number control by showing that autorepression-defective initiator mutants also can elevate the plasmid copy number. We further show, by quantitative modeling, that initiator dimerization is a homeostatic mechanism that dampens active monomer increase when the protein is oversupplied. This finding implies that oversupplied initiator proteins are largely dimeric, partly accounting for their limited ability to increase copy number. A combination of autorepression, dimerization, and handcuffing appears to account fully for control of P1 plasmid copy number.autorepression ͉ DNA replication control ͉ homeostatic control ͉ plasmid copy number control

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“…Initiator titration is in turn counteracted by both dimerization and autorepression, unless handcuffing ensures that the titrated initiators in their bound state can participate in control (24,47). In fact, the same control-defective mutants that show increased replication initiation (the copy-up phenotype) can be defective in all three processes of autorepression, dimerization, and handcuffing, as would be expected from their interdependence (48). Such tightly interwoven systems are particularly challenging to analyze, and the relative importance of the different control steps is not known, although the handcuffing interaction is considered necessary.…”

Section: Common Ground In Replication Control Of Iteron-based Plasmidmentioning

confidence: 99%

Random versus Cell Cycle-Regulated Replication Initiation in Bacteria: Insights from Studying Vibrio cholerae Chromosome 2

Ramachandran

Jha

Paulsson

et al. 2017

Microbiol Mol Biol Rev

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SUMMARY Bacterial chromosomes initiate replication at a fixed time in the cell cycle, whereas there is generally no particular time for plasmid replication initiation or chromosomal replication initiation from integrated plasmids. In bacteria with divided genomes, the replication system of one of the chromosomes typically resembles that of bacteria with undivided genomes, whereas the remaining chromosomes have plasmid-like replication systems. For example, in Vibrio cholerae, a bacterium with two chromosomes (chromosome 1 [Chr1] and Chr2), the Chr1 system resembles that of the Escherichia coli chromosome, and the Chr2 system resembles that of iteron-based plasmids. However, Chr2 still initiates replication at a fixed time in the cell cycle and thus offers an opportunity to understand the molecular basis for the difference between random and cell cycle-regulated modes of replication. Here we review studies of replication control in Chr2 and compare it to those of plasmids and chromosomes. We argue that although the Chr2 control mechanisms in many ways are reminiscent of those of plasmids, they also appear to combine more regulatory features than are found on a typical plasmid, including some that are more typical of chromosomes. One of the regulatory mechanisms is especially novel, the coordinated timing of replication initiation of Chr1 and Chr2, providing the first example of communication between chromosomes for replication initiation.

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Chaperone‐mediated reduction of RepA dimerization is associated with RepA conformational change

Cited by 25 publications

References 38 publications

Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p)

Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p)

Multiple homeostatic mechanisms in the control of P1 plasmid replication

Random versus Cell Cycle-Regulated Replication Initiation in Bacteria: Insights from Studying Vibrio cholerae Chromosome 2

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