Sequence-independent DNA binding and replication initiation by the human origin recognition complex

Sanjay Vashee, Christin Cvetic, Wenyan Lu, Pamela Simancek, Thomas J. Kelly, Johannes C. Walter

Research output: Contribution to journalArticlepeer-review

213 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1894-1908
Number of pages15
JournalGenes and Development
Issue number15
StatePublished - Aug 1 2003
Externally publishedYes


  • DNA replication
  • DNA-binding specificity
  • Origin of DNA replication
  • Origin recognition complex

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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