Coordinate Binding of ATP and Origin DNA Regulates the ATPase Activity of the Origin Recognition Complex

Klemm, Richard D.; Austin, Robert J.; Bell, Stephen P.

doi:10.1016/s0092-8674(00)81889-9

Cited by 228 publications

(319 citation statements)

References 41 publications

(8 reference statements)

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“…The fact that the D2 domains bind ATP approximately 100-fold higher than ADP is consistent with other nucleotide binding proteins that lack ATPase activity (45). Unlike the D1 domain, the amino acid sequence of the D2 ATP-binding site is only distantly related to the 240 amino acid consensus ATP-binding sites of the ATPases associated with a variety of cellular activities (AAA) family; therefore the D2 domain may not have the ATPase activity or the associated force-generating capacity predicted for the other AAA protein (46).…”

Section: Discussionsupporting

confidence: 82%

N-Ethylmaleimide-sensitive Fusion Protein Contains High and Low Affinity ATP-binding Sites That Are Functionally Distinct

Matveeva

Whiteheart

1997

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 82%

N-Ethylmaleimide-sensitive Fusion Protein Contains High and Low Affinity ATP-binding Sites That Are Functionally Distinct

Matveeva

Whiteheart

1997

Journal of Biological Chemistry

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“…(10) The ATPase activity or ORC is inhibited by dsDNA and is stimulated by ssDNA, suggesting that it may be activated after origin unwinding. (17) Although the replicator sequences in other eukarya are larger and less defined than in S. cerevisiae, ORC has been conserved during evolution and is required for initiation of DNA replication in different species. (16) In Xenopus, Drosophila melanogaster and mammalian cells, ORC associates with the chromatin, (18)(19)(20)(21)(22) but its binding sites are poorly defined.…”

Section: Introductionmentioning

confidence: 99%

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

2003

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SummaryThe hardest part of replicating a genome is the beginning. The first step of DNA replication (called ''initiation'') mobilizes a large number of specialized proteins (''initiators'') that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ringshaped helicase onto the DNA double helix.

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“…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)(7)(8). However, structural similarities have been found among some of the accessory factors of prokaryotic and eukaryotic replicative DNA polymerases (9)(10)(11).…”

mentioning

confidence: 99%

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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Coordinate Binding of ATP and Origin DNA Regulates the ATPase Activity of the Origin Recognition Complex

Cited by 228 publications

References 41 publications

N-Ethylmaleimide-sensitive Fusion Protein Contains High and Low Affinity ATP-binding Sites That Are Functionally Distinct

N-Ethylmaleimide-sensitive Fusion Protein Contains High and Low Affinity ATP-binding Sites That Are Functionally Distinct

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

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

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