Sphingosine inhibits the synthesis of RNA primers by primase in vitro.
Identifieur interne : 002882 ( Ncbi/Merge ); précédent : 002881; suivant : 002883Sphingosine inhibits the synthesis of RNA primers by primase in vitro.
Auteurs : C M Simbulan [Japon] ; K. Tamiya-Koizumi ; M. Suzuki ; M. Shoji ; T. Taki ; S. YoshidaSource :
- Biochemistry [ 0006-2960 ] ; 1994.
Descripteurs français
- KwdFr :
- MESH :
- antagonistes et inhibiteurs : RNA nucleotidyltransferases.
- biosynthèse : ARN.
- métabolisme : ADN, RNA nucleotidyltransferases.
- pharmacologie : Sphingosine.
- ARN bactérien, Animaux, Bovins, DNA primase, Relation dose-effet des médicaments, Spécificité du substrat.
English descriptors
- KwdEn :
- MESH :
- chemical , antagonists & inhibitors : RNA Nucleotidyltransferases.
- chemical , biosynthesis : RNA.
- chemical , metabolism : DNA, RNA Nucleotidyltransferases.
- chemical , pharmacology : Sphingosine.
- Animals, Cattle, DNA Primase, Dose-Response Relationship, Drug, RNA, Bacterial, Substrate Specificity.
Abstract
We have previously shown the presence of sphingomyelin and sphingomyelinase in cell nuclei, suggesting that they may play a role in the intranuclear production of sphingosine, a potent bioactive molecule modulating diverse cellular functions. In the present study, the direct effects of sphingosine (C18:1) on the activity of DNA replication/repair polymerases were studied in vitro. Sphingosine had no effect on DNA polymerases alpha and beta and slightly inhibited DNA polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly inhibited the activity of primase in a dose-dependent manner. On the other hand, dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no effect on primase activity. Sphingosine equally inhibited the activity of primase complexed with DNA polymerase alpha, as well as its free form, with a Ki value of 4 microM. A gel-retardation analysis showed that the binding of primase with 32P-labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was competitive with the DNA template, but not with the substrate NTPs. After product analysis, a dose-dependent decrease in the amount of RNA primer products, consisting mainly of 10- and 11-mers, was observed in the presence of sphingosine, indicating that it inhibits the synthesis of RNA primers by primase. Sphingosine, however, had no effect on T7 RNA polymerase.
DOI: 10.1021/bi00196a019
PubMed: 7519054
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sphingosine inhibits the synthesis of RNA primers by primase in vitro.</title><author><name sortKey="Simbulan, C M" sort="Simbulan, C M" uniqKey="Simbulan C" first="C M" last="Simbulan">C M Simbulan</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi</wicri:regionArea><wicri:noRegion>Aichi</wicri:noRegion></affiliation></author><author><name sortKey="Tamiya Koizumi, K" sort="Tamiya Koizumi, K" uniqKey="Tamiya Koizumi K" first="K" last="Tamiya-Koizumi">K. Tamiya-Koizumi</name></author><author><name sortKey="Suzuki, M" sort="Suzuki, M" uniqKey="Suzuki M" first="M" last="Suzuki">M. Suzuki</name></author><author><name sortKey="Shoji, M" sort="Shoji, M" uniqKey="Shoji M" first="M" last="Shoji">M. Shoji</name></author><author><name sortKey="Taki, T" sort="Taki, T" uniqKey="Taki T" first="T" last="Taki">T. Taki</name></author><author><name sortKey="Yoshida, S" sort="Yoshida, S" uniqKey="Yoshida S" first="S" last="Yoshida">S. Yoshida</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1994">1994</date><idno type="RBID">pubmed:7519054</idno><idno type="pmid">7519054</idno><idno type="doi">10.1021/bi00196a019</idno><idno type="wicri:Area/PubMed/Corpus">002870</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002870</idno><idno type="wicri:Area/PubMed/Curation">002870</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002870</idno><idno type="wicri:Area/PubMed/Checkpoint">002712</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002712</idno><idno type="wicri:Area/Ncbi/Merge">002882</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Sphingosine inhibits the synthesis of RNA primers by primase in vitro.</title><author><name sortKey="Simbulan, C M" sort="Simbulan, C M" uniqKey="Simbulan C" first="C M" last="Simbulan">C M Simbulan</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi</wicri:regionArea><wicri:noRegion>Aichi</wicri:noRegion></affiliation></author><author><name sortKey="Tamiya Koizumi, K" sort="Tamiya Koizumi, K" uniqKey="Tamiya Koizumi K" first="K" last="Tamiya-Koizumi">K. Tamiya-Koizumi</name></author><author><name sortKey="Suzuki, M" sort="Suzuki, M" uniqKey="Suzuki M" first="M" last="Suzuki">M. Suzuki</name></author><author><name sortKey="Shoji, M" sort="Shoji, M" uniqKey="Shoji M" first="M" last="Shoji">M. Shoji</name></author><author><name sortKey="Taki, T" sort="Taki, T" uniqKey="Taki T" first="T" last="Taki">T. Taki</name></author><author><name sortKey="Yoshida, S" sort="Yoshida, S" uniqKey="Yoshida S" first="S" last="Yoshida">S. Yoshida</name></author></analytic><series><title level="j">Biochemistry</title><idno type="ISSN">0006-2960</idno><imprint><date when="1994" type="published">1994</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cattle</term><term>DNA (metabolism)</term><term>DNA Primase</term><term>Dose-Response Relationship, Drug</term><term>RNA (biosynthesis)</term><term>RNA Nucleotidyltransferases (antagonists & inhibitors)</term><term>RNA Nucleotidyltransferases (metabolism)</term><term>RNA, Bacterial</term><term>Sphingosine (pharmacology)</term><term>Substrate Specificity</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (métabolisme)</term><term>ARN (biosynthèse)</term><term>ARN bactérien</term><term>Animaux</term><term>Bovins</term><term>DNA primase</term><term>RNA nucleotidyltransferases (antagonistes et inhibiteurs)</term><term>RNA nucleotidyltransferases (métabolisme)</term><term>Relation dose-effet des médicaments</term><term>Sphingosine (pharmacologie)</term><term>Spécificité du substrat</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>RNA Nucleotidyltransferases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA</term><term>RNA Nucleotidyltransferases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Sphingosine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>RNA nucleotidyltransferases</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN</term><term>RNA nucleotidyltransferases</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Sphingosine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cattle</term><term>DNA Primase</term><term>Dose-Response Relationship, Drug</term><term>RNA, Bacterial</term><term>Substrate Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN bactérien</term><term>Animaux</term><term>Bovins</term><term>DNA primase</term><term>Relation dose-effet des médicaments</term><term>Spécificité du substrat</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have previously shown the presence of sphingomyelin and sphingomyelinase in cell nuclei, suggesting that they may play a role in the intranuclear production of sphingosine, a potent bioactive molecule modulating diverse cellular functions. In the present study, the direct effects of sphingosine (C18:1) on the activity of DNA replication/repair polymerases were studied in vitro. Sphingosine had no effect on DNA polymerases alpha and beta and slightly inhibited DNA polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly inhibited the activity of primase in a dose-dependent manner. On the other hand, dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no effect on primase activity. Sphingosine equally inhibited the activity of primase complexed with DNA polymerase alpha, as well as its free form, with a Ki value of 4 microM. A gel-retardation analysis showed that the binding of primase with 32P-labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was competitive with the DNA template, but not with the substrate NTPs. After product analysis, a dose-dependent decrease in the amount of RNA primer products, consisting mainly of 10- and 11-mers, was observed in the presence of sphingosine, indicating that it inhibits the synthesis of RNA primers by primase. Sphingosine, however, had no effect on T7 RNA polymerase.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">7519054</PMID><DateCompleted><Year>1994</Year><Month>09</Month><Day>01</Day></DateCompleted><DateRevised><Year>2019</Year><Month>06</Month><Day>13</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0006-2960</ISSN><JournalIssue CitedMedium="Print"><Volume>33</Volume><Issue>30</Issue><PubDate><Year>1994</Year><Month>Aug</Month><Day>02</Day></PubDate></JournalIssue><Title>Biochemistry</Title><ISOAbbreviation>Biochemistry</ISOAbbreviation></Journal><ArticleTitle>Sphingosine inhibits the synthesis of RNA primers by primase in vitro.</ArticleTitle><Pagination><MedlinePgn>9007-12</MedlinePgn></Pagination><Abstract><AbstractText>We have previously shown the presence of sphingomyelin and sphingomyelinase in cell nuclei, suggesting that they may play a role in the intranuclear production of sphingosine, a potent bioactive molecule modulating diverse cellular functions. In the present study, the direct effects of sphingosine (C18:1) on the activity of DNA replication/repair polymerases were studied in vitro. Sphingosine had no effect on DNA polymerases alpha and beta and slightly inhibited DNA polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly inhibited the activity of primase in a dose-dependent manner. On the other hand, dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no effect on primase activity. Sphingosine equally inhibited the activity of primase complexed with DNA polymerase alpha, as well as its free form, with a Ki value of 4 microM. A gel-retardation analysis showed that the binding of primase with 32P-labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was competitive with the DNA template, but not with the substrate NTPs. After product analysis, a dose-dependent decrease in the amount of RNA primer products, consisting mainly of 10- and 11-mers, was observed in the presence of sphingosine, indicating that it inhibits the synthesis of RNA primers by primase. Sphingosine, however, had no effect on T7 RNA polymerase.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Simbulan</LastName><ForeName>C M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Laboratory of Cancer Cell Biology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tamiya-Koizumi</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Suzuki</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Shoji</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Taki</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Yoshida</LastName><ForeName>S</ForeName><Initials>S</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biochemistry</MedlineTA><NlmUniqueID>0370623</NlmUniqueID><ISSNLinking>0006-2960</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C034477">RNA primers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012329">RNA, Bacterial</NameOfSubstance></Chemical><Chemical><RegistryNumber>63231-63-0</RegistryNumber><NameOfSubstance UI="D012313">RNA</NameOfSubstance></Chemical><Chemical><RegistryNumber>9007-49-2</RegistryNumber><NameOfSubstance UI="D004247">DNA</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.7.-</RegistryNumber><NameOfSubstance UI="D019915">DNA Primase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.7.-</RegistryNumber><NameOfSubstance UI="D012316">RNA Nucleotidyltransferases</NameOfSubstance></Chemical><Chemical><RegistryNumber>NGZ37HRE42</RegistryNumber><NameOfSubstance UI="D013110">Sphingosine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002417" MajorTopicYN="N">Cattle</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004247" MajorTopicYN="N">DNA</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019915" MajorTopicYN="N">DNA Primase</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012313" MajorTopicYN="N">RNA</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012316" MajorTopicYN="N">RNA Nucleotidyltransferases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012329" MajorTopicYN="N">RNA, Bacterial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013110" MajorTopicYN="N">Sphingosine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1994</Year><Month>8</Month><Day>2</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1994</Year><Month>8</Month><Day>2</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1994</Year><Month>8</Month><Day>2</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">7519054</ArticleId><ArticleId IdType="doi">10.1021/bi00196a019</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Japon</li></country></list><tree><noCountry><name sortKey="Shoji, M" sort="Shoji, M" uniqKey="Shoji M" first="M" last="Shoji">M. Shoji</name><name sortKey="Suzuki, M" sort="Suzuki, M" uniqKey="Suzuki M" first="M" last="Suzuki">M. Suzuki</name><name sortKey="Taki, T" sort="Taki, T" uniqKey="Taki T" first="T" last="Taki">T. Taki</name><name sortKey="Tamiya Koizumi, K" sort="Tamiya Koizumi, K" uniqKey="Tamiya Koizumi K" first="K" last="Tamiya-Koizumi">K. Tamiya-Koizumi</name><name sortKey="Yoshida, S" sort="Yoshida, S" uniqKey="Yoshida S" first="S" last="Yoshida">S. Yoshida</name></noCountry><country name="Japon"><noRegion><name sortKey="Simbulan, C M" sort="Simbulan, C M" uniqKey="Simbulan C" first="C M" last="Simbulan">C M Simbulan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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