Inhibitory effects of acidic phospholipids on the binding of origin-recognition complex to origin DNA

Jong Ryul Lee, Masaki Makise, Hitomi Takenaka, Naoko Takahashi, Yoshihiro Yamaguchi, Tomofusa Tsuchiya, Tohru Mizushima

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8 Citations (Scopus)

Abstract

Origin-recognition complex (ORC), a candidate initiator of chromosomal DNA replication in eukaryotes, shares certain biochemical characteristics with DnaA, the initiator of chromosomal DNA replication in prokaryotes. These similarities include origin-specific DNA binding, ATP binding and ATPase activity. DnaA interacts with acidic phospholipids, such as cardiolipin, and its activity is regulated by these phospholipids. In this study, we examined whether Saccharomyces cerevisiae ORC also interacts with phospholipids. Among the various phospholipids tested, ORC was found to bind specifically to cardiolipin. This binding was inhibited by excess concentrations of salts but unaffected by ATP, adenosine 5′-[γ-thio]triphosphate or the origin DNA. Cardiolipin weakly inhibited the ATP-binding activity of ORC, whereas it strongly inhibited ORC binding to origin DNA. Acidic phospholipids other than cardiolipin (phosphatidylglycerol and phosphatidylinositol) weakly inhibited ORC binding to origin DNA. Furthermore, total phospholipids extracted from yeast nuclear membranes inhibited ORC binding to origin DNA. We consider that phospholipids may modulate initiation of DNA replication in eukaryotes in a similar manner to that found in prokaryotes.

Original languageEnglish
Pages (from-to)395-399
Number of pages5
JournalBiochemical Journal
Volume362
Issue number2
DOIs
Publication statusPublished - 2002 Mar 1

Keywords

  • ATP binding
  • Cardiolipin
  • DNA replication
  • DnaA
  • Origin binding

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lee, J. R., Makise, M., Takenaka, H., Takahashi, N., Yamaguchi, Y., Tsuchiya, T., & Mizushima, T. (2002). Inhibitory effects of acidic phospholipids on the binding of origin-recognition complex to origin DNA. Biochemical Journal, 362(2), 395-399. https://doi.org/10.1042/bj3620395