Document Detail

Acidic phospholipids with unsaturated fatty acids inhibit the binding of origin recognition complex to origin DNA.
MedLine Citation:
PMID:  11926991     Owner:  NLM     Status:  MEDLINE    
Origin Recognition Complex (ORC) is a candidate initiator of chromosomal DNA replication in eukaryotes. We recently reported that cardiolipin inhibits the interaction of Origin Recognition Complex ORC with origin DNA, as is the case of DnaA, the initiator of chromosomal DNA replication in prokaryotes. We report here that another acidic phospholipid, phosphatidylglycerol (PG), also inhibits the interaction. Synthetic PG with only unsaturated fatty acids inhibits ORC-binding to origin DNA more strongly than PG with only saturated fatty acids. On the other hand, phosphatidylcholine (neutral phospholipid) does not affect the ORC-origin interaction, regardless of the presence of saturated or unsaturated fatty acids. These results suggest that an acidic moiety and unsaturated fatty acids are important factors for the inhibitory effect of phospholipids on ORC binding to origin DNA, as is the case for DnaA. The inhibitory effect of cardiolipin on ORC binding to origin DNA was more apparent at 30 degrees C than at 4 degrees C. Furthermore, chlorpromazine restored the ORC-origin interaction in the presence of cardiolipin. Since the presence of unsaturated fatty acids, low incubation temperatures, and the addition of chlorpromazine all decrease membrane fluidity, these results suggest that membrane fluidity is important for the inhibitory effect of acidic phospholipids on ORC-binding to origin DNA, as is the case for DnaA.
Jong-Ryul Lee; Hitomi Takenaka; Naoko Takahashi; Masaki Makise; Yoshihiro Yamaguchi; Tomofusa Tsuchiya; Tohru Mizushima
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biochemistry     Volume:  131     ISSN:  0021-924X     ISO Abbreviation:  J. Biochem.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-02     Completed Date:  2002-10-09     Revised Date:  2007-12-19    
Medline Journal Info:
Nlm Unique ID:  0376600     Medline TA:  J Biochem     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  541-6     Citation Subset:  IM    
Faculty of Pharmaceutical Sciences, Okayama University, 700-8530, Japan.
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MeSH Terms
Adenosine Triphosphate / metabolism
Cardiolipins / metabolism
Cell Line
Chlorpromazine / pharmacology
DNA / metabolism
Dopamine Antagonists / pharmacology
Dose-Response Relationship, Drug
Fatty Acids / metabolism
Fatty Acids, Unsaturated / metabolism
Phospholipids / metabolism*
Precipitin Tests
Protein Binding
Replication Origin
Saccharomyces cerevisiae / metabolism
Time Factors
Reg. No./Substance:
0/Cardiolipins; 0/Dopamine Antagonists; 0/Fatty Acids; 0/Fatty Acids, Unsaturated; 0/Phospholipids; 50-53-3/Chlorpromazine; 56-65-5/Adenosine Triphosphate; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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