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Sequence-independent DNA binding and replication initiation by the human origin recognition complex
Open accessAbstract
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.
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Cited by
Mechanisms for initiating cellular DNA replication
Bleichert, F., Botchan, M. R., & Berger, J. M. (2017) · Science · doi:10.1126/science.aah6317 · Cited by 220
Ribonucleotide incorporation into DNA during DNA replication and its consequences
Zhou, Z.-X., Williams, J. S., Lujan, S. A., & Kunkel, T. A. (2021) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2020.1869175 · Cited by 30
Metadata
- Authors
- Vashee, S., Cvetic, C., Lu, W., Simancek, P., Kelly, T. J., & Walter, J. C.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-08-01
- Volume
- 17
- Issue
- 15
- Pages
- 1894-1908
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2099117602
- Cited by
- 322
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Vashee, S., Cvetic, C., Lu, W., Simancek, P., Kelly, T. J., & Walter, J. C. (2003). Sequence-independent DNA binding and replication initiation by the human origin recognition complex. Genes & Development. https://doi.org/10.1101/gad.1084203
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