Interaction of Human Telomerase with Its Primer Substrate
Identifieur interne : 003243 ( Main/Exploration ); précédent : 003242; suivant : 003244Interaction of Human Telomerase with Its Primer Substrate
Auteurs : Gerald Wallweber [États-Unis] ; Sergei Gryaznov [États-Unis] ; Krisztina Pongracz [États-Unis] ; Ronald Pruzan [États-Unis, Oman]Source :
- Biochemistry [ 0006-2960 ] ; 2002.
Abstract
Telomerase is a ribonucleoprotein responsible for maintaining the ends of linear chromosomes in nearly all eukaryotic cells. In humans, expression of the enzyme is limited primarily to the germ line and progenitor cell populations. In the absence of telomerase activity, telomeres shorten with each cell division until a critical length is reached, which can result in the cessation of cell division. The enzyme is required for cell immortality, and its activity has been detected in the vast majority of human tumors. Because of this, telomerase is an attractive target for inhibition in anticancer therapy. To learn more about the biochemistry of the human enzyme and its substrate recognition, we have examined the binding properties of single-stranded oligonucleotide primers that serve as telomerase substrates in vitro. We have used highly purified human enzyme and employed a two-primer method for determining the dissociation rates of these primers. Primers having sequence permutations of (TTAGGG)3 were found to have considerably different affinities. They had t1/2 values that ranged from 14 min to greater than 1200 min at room temperature. A primer ending in the GGG register formed the most stable complex with the enzyme. This particular register imparted stability to a nontelomeric primer resulting in a nearly 100-fold decrease in the koff. We have found that interactions of telomerase with primer substrates are stabilized mainly by contacts with the protein subunit of the enzyme (hTERT). Base-pairing between the primer and the template region of telomerase contributes minimally to its stabilization.
Url:
DOI: 10.1021/bi026914a
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 002229
- to stream Istex, to step Curation: 002229
- to stream Istex, to step Checkpoint: 000C48
- to stream Main, to step Merge: 003278
- to stream Main, to step Curation: 003243
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Interaction of Human Telomerase with Its Primer Substrate</title><author><name sortKey="Wallweber, Gerald" sort="Wallweber, Gerald" uniqKey="Wallweber G" first="Gerald" last="Wallweber">Gerald Wallweber</name></author><author><name sortKey="Gryaznov, Sergei" sort="Gryaznov, Sergei" uniqKey="Gryaznov S" first="Sergei" last="Gryaznov">Sergei Gryaznov</name></author><author><name sortKey="Pongracz, Krisztina" sort="Pongracz, Krisztina" uniqKey="Pongracz K" first="Krisztina" last="Pongracz">Krisztina Pongracz</name></author><author><name sortKey="Pruzan, Ronald" sort="Pruzan, Ronald" uniqKey="Pruzan R" first="Ronald" last="Pruzan">Ronald Pruzan</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D7E0CBE8517B444878A78467DFE6F3A10ED366A8</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1021/bi026914a</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-P2TXNQ9N-G/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">002229</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002229</idno><idno type="wicri:Area/Istex/Curation">002229</idno><idno type="wicri:Area/Istex/Checkpoint">000C48</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000C48</idno><idno type="wicri:doubleKey">0006-2960:2003:Wallweber G:interaction:of:human</idno><idno type="wicri:Area/Main/Merge">003278</idno><idno type="wicri:Area/Main/Curation">003243</idno><idno type="wicri:Area/Main/Exploration">003243</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Interaction of Human Telomerase with Its Primer Substrate</title><author><name sortKey="Wallweber, Gerald" sort="Wallweber, Gerald" uniqKey="Wallweber G" first="Gerald" last="Wallweber">Gerald Wallweber</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Geron Corporation, 230 Constitution Drive, Menlo Park</wicri:cityArea></affiliation></author><author><name sortKey="Gryaznov, Sergei" sort="Gryaznov, Sergei" uniqKey="Gryaznov S" first="Sergei" last="Gryaznov">Sergei Gryaznov</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Geron Corporation, 230 Constitution Drive, Menlo Park</wicri:cityArea></affiliation></author><author><name sortKey="Pongracz, Krisztina" sort="Pongracz, Krisztina" uniqKey="Pongracz K" first="Krisztina" last="Pongracz">Krisztina Pongracz</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Geron Corporation, 230 Constitution Drive, Menlo Park</wicri:cityArea></affiliation></author><author><name sortKey="Pruzan, Ronald" sort="Pruzan, Ronald" uniqKey="Pruzan R" first="Ronald" last="Pruzan">Ronald Pruzan</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Geron Corporation, 230 Constitution Drive, Menlo Park</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Oman</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Biochemistry</title><title level="j" type="abbrev">Biochemistry</title><idno type="ISSN">0006-2960</idno><idno type="eISSN">1520-4995</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2002</date><date type="published">2003</date><biblScope unit="vol">42</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="589">589</biblScope><biblScope unit="page" to="600">600</biblScope></imprint><idno type="ISSN">0006-2960</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2960</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Telomerase is a ribonucleoprotein responsible for maintaining the ends of linear chromosomes in nearly all eukaryotic cells. In humans, expression of the enzyme is limited primarily to the germ line and progenitor cell populations. In the absence of telomerase activity, telomeres shorten with each cell division until a critical length is reached, which can result in the cessation of cell division. The enzyme is required for cell immortality, and its activity has been detected in the vast majority of human tumors. Because of this, telomerase is an attractive target for inhibition in anticancer therapy. To learn more about the biochemistry of the human enzyme and its substrate recognition, we have examined the binding properties of single-stranded oligonucleotide primers that serve as telomerase substrates in vitro. We have used highly purified human enzyme and employed a two-primer method for determining the dissociation rates of these primers. Primers having sequence permutations of (TTAGGG)3 were found to have considerably different affinities. They had t1/2 values that ranged from 14 min to greater than 1200 min at room temperature. A primer ending in the GGG register formed the most stable complex with the enzyme. This particular register imparted stability to a nontelomeric primer resulting in a nearly 100-fold decrease in the koff. We have found that interactions of telomerase with primer substrates are stabilized mainly by contacts with the protein subunit of the enzyme (hTERT). Base-pairing between the primer and the template region of telomerase contributes minimally to its stabilization.</div></front></TEI><affiliations><list><country><li>Oman</li><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Wallweber, Gerald" sort="Wallweber, Gerald" uniqKey="Wallweber G" first="Gerald" last="Wallweber">Gerald Wallweber</name></region><name sortKey="Gryaznov, Sergei" sort="Gryaznov, Sergei" uniqKey="Gryaznov S" first="Sergei" last="Gryaznov">Sergei Gryaznov</name><name sortKey="Pongracz, Krisztina" sort="Pongracz, Krisztina" uniqKey="Pongracz K" first="Krisztina" last="Pongracz">Krisztina Pongracz</name><name sortKey="Pruzan, Ronald" sort="Pruzan, Ronald" uniqKey="Pruzan R" first="Ronald" last="Pruzan">Ronald Pruzan</name></country><country name="Oman"><noRegion><name sortKey="Pruzan, Ronald" sort="Pruzan, Ronald" uniqKey="Pruzan R" first="Ronald" last="Pruzan">Ronald Pruzan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003243 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003243 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:D7E0CBE8517B444878A78467DFE6F3A10ED366A8
|texte= Interaction of Human Telomerase with Its Primer Substrate
}}
| This area was generated with Dilib version V0.6.33. |  |