Publication Date:
2011-10-04
Description:
Many replication initiators form higher-order oligomers that process host replication origins to promote replisome formation. In addition to dedicated duplex-DNA-binding domains, cellular initiators possess AAA+ (ATPases associated with various cellular activities) elements that drive functions ranging from protein assembly to origin recognition. In bacteria, the AAA+ domain of the initiator DnaA has been proposed to assist in single-stranded DNA formation during origin melting. Here we show crystallographically and in solution that the ATP-dependent assembly of Aquifex aeolicus DnaA into a spiral oligomer creates a continuous surface that allows successive AAA+ domains to bind and extend single-stranded DNA segments. The mechanism of binding is unexpectedly similar to that of RecA, a homologous recombination factor, but it differs in that DnaA promotes a nucleic acid conformation that prevents pairing of a complementary strand. These findings, combined with strand-displacement assays, indicate that DnaA opens replication origins by a direct ATP-dependent stretching mechanism. Comparative studies reveal notable commonalities between the approach used by DnaA to engage DNA substrates and other, nucleic-acid-dependent, AAA+ systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192921/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192921/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duderstadt, Karl E -- Chuang, Kevin -- Berger, James M -- GM071747/GM/NIGMS NIH HHS/ -- R01 GM071747/GM/NIGMS NIH HHS/ -- R01 GM071747-06/GM/NIGMS NIH HHS/ -- T32 GM008295/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Oct 2;478(7368):209-13. doi: 10.1038/nature10455.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Graduate Group, University of California, Berkeley, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21964332" target="_blank"〉PubMed〈/a〉
Keywords:
AT Rich Sequence
;
Adenosine Triphosphatases/metabolism
;
Adenosine Triphosphate/metabolism
;
Bacteria/enzymology/genetics
;
Bacterial Proteins/chemistry/*metabolism
;
Biocatalysis
;
Crystallography, X-Ray
;
DNA Replication
;
DNA, Bacterial/*chemistry/genetics/*metabolism
;
DNA, Single-Stranded/chemistry/genetics/metabolism
;
DNA-Binding Proteins/chemistry/*metabolism
;
DNA-Directed DNA Polymerase/metabolism
;
Models, Molecular
;
Molecular Conformation
;
Multienzyme Complexes/metabolism
;
*Nucleic Acid Conformation
;
Nucleic Acid Denaturation
;
Rec A Recombinases/chemistry
;
*Replication Origin/genetics
;
Substrate Specificity
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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