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-depletedXenopusegg 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.
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Dates
Type | When |
---|---|
Created | 22 years, 1 month ago (Aug. 1, 2003, 1:28 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 15, 2021, 10:17 p.m.) |
Indexed | 1 month, 1 week ago (July 22, 2025, 6:59 a.m.) |
Issued | 22 years, 1 month ago (Aug. 1, 2003) |
Published | 22 years, 1 month ago (Aug. 1, 2003) |
Published Online | 22 years, 1 month ago (Aug. 1, 2003) |
Published Print | 22 years, 1 month ago (Aug. 1, 2003) |
@article{Vashee_2003, title={Sequence-independent DNA binding and replication initiation by the human origin recognition complex}, volume={17}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1084203}, DOI={10.1101/gad.1084203}, number={15}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Vashee, Sanjay and Cvetic, Christin and Lu, Wenyan and Simancek, Pamela and Kelly, Thomas J. and Walter, Johannes C.}, year={2003}, month=aug, pages={1894–1908} }