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Genes Dev August 1, 2003; 17 (15): 1894-908.

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

Vashee S , Cvetic C , Lu W , Simancek P , Kelly TJ , Walter JC .

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.

PubMed ID: 12897055
PMC ID: PMC196240
Article link: Genes Dev
Grant support: [+]

References [+] :
Abdurashidova, Start sites of bidirectional DNA synthesis at the human lamin B2 origin. 2000, Pubmed

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