The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo

Kohji Noguchi, Alex Vassilev, Soma Ghosh, John L. Yates, Melvin L. DePamphilis

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65 Citations (Scopus)

Abstract

Selection of initiation sites for DNA replication in eukaryotes is determined by the interaction between the origin recognition complex (ORC) and genomic DNA. In mammalian cells, this interaction appears to be regulated by Orc1, the only ORC subunit that contains a bromo-adjacent homology (BAH) domain. Since BAH domains mediate protein-protein interactions, the human Orc1 BAH domain was mutated, and the mutant proteins expressed in human cells to determine their affects on ORC function. The BAH domain was not required for nuclear localization of Orc1, association of Orc1 with other ORC subunits, or selective degradation of Orc1 during S-phase. It did, however, facilitate reassociation of Orc1 with chromosomes during the M to G1-phase transition, and it was required for binding Orc1 to the Epstein-Barr virus oriP and stimulating oriP-dependent plasmid DNA replication. Moreover, the BAH domain affected Orc1's ability to promote binding of Orc2 to chromatin as cells exit mitosis. Thus, the BAH domain in human Orc1 facilitates its ability to activate replication origins in vivo by promoting association of ORC with chromatin.

Original languageEnglish
Pages (from-to)5372-5382
Number of pages11
JournalEMBO Journal
Volume25
Issue number22
DOIs
Publication statusPublished - 2006 Nov 15

Keywords

  • Cell cycle
  • DNA replication
  • Epstein-Barr virus
  • Origin recognition complex
  • oriP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Noguchi, K., Vassilev, A., Ghosh, S., Yates, J. L., & DePamphilis, M. L. (2006). The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo. EMBO Journal, 25(22), 5372-5382. https://doi.org/10.1038/sj.emboj.7601396