Sequence-independent DNA binding and replication initiation by the human origin recognition complex Journal Article
| Authors: | Vashee, S.; Cvetic, C.; Lu, W.; Simancek, P.; Kelly, T. J.; Walter, J. C. |
| Article Title: | Sequence-independent DNA binding and replication initiation by the human origin recognition complex |
| Abstract: | We report that a highly purified human origin recognition complex (HsORC) has intrinsic DNA-binding activity, and that this activity is modestly stimulated by ATP. HsORC binds preferentially to synthetic AT-rich polydeoxynucleotides, but does not effectively discriminate between natural DNA fragments that contain known human origins and control fragments. The complex fully restores DNA replication to ORC-depleted Xenopus egg extracts, providing strong evidence for its initiator function. Strikingly, HsORC stimulates initiation from any DNA sequence, and it does not preferentially replicate DNA containing human origin sequences. These data provide a biochemical explanation for the observation that in metazoans, initiation of DNA replication often occurs in a seemingly random pattern, and they have important implications for the nature of human origins of DNA replication. |
| Keywords: | controlled study; unclassified drug; dna-binding proteins; nonhuman; dna replication; protein function; animal cell; animals; cell line; protein; protein binding; dose-response relationship, drug; time factors; animalia; dna; protein purification; protein synthesis; extract; nucleotide sequence; recombinant proteins; plasmids; dna sequence; adenosine triphosphate; dna binding; xenopus; metazoa; dna fragment; stimulation; insects; binding, competitive; origin recognition complex; cell-free system; humans; priority journal; article; at rich sequence; dna-binding specificity; origin of dna replication; human origin recognition complex; polydeoxyribonucleotide |
| Journal Title: | Genes and Development |
| Volume: | 17 |
| Issue: | 15 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2003-08-01 |
| Start Page: | 1894 |
| End Page: | 1908 |
| Language: | English |
| DOI: | 10.1101/gad.1084203 |
| PUBMED: | 12897055 |
| PROVIDER: | scopus |
| PMCID: | PMC196240 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Molecular Sequence Numbers: GENBANK: M94363; -- Source: Scopus |
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