Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest
Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3′–5′ DNA h...
Gespeichert in:
| Veröffentlicht in: | EMBO reports 2000-07, Vol.1 (1), p.80-84 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 84 |
|---|---|
| container_issue | 1 |
| container_start_page | 80 |
| container_title | EMBO reports |
| container_volume | 1 |
| creator | Constantinou, Angelos Tarsounas, Madalena Karow, Julia K Brosh, Robert M Bohr, Vilhelm A Hickson, Ian D West, Stephen C |
| description | Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The
WRN
gene encodes a 3′–5′ DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (
BLM
). In this work, we show that WRN promotes the ATP‐dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S‐phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single‐stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates. |
| doi_str_mv | 10.1093/embo-reports/kvd004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1083680</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>373527301</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5602-99850cfb7c8f979c3fc1314eff70d39376b35f871aa8eff37593360752d7b6ae3</originalsourceid><addsrcrecordid>eNqNkUtv1DAUhSMEog_4BUjIYkFhEWrH49cGqVRlijSUagSa7izHcaaeJnawk5bh1-NRohZYIFa27O-ce65Olr1A8B2CAh-btvR5MJ0PfTy-ua0gnD3K9tGMihwjxh9P96JAV3vZQYwbCCERjD_N9hAqCKUY7mftygRnwlEEceuq4FsDuuB7Yx14s1pevAWtXQfVmwjOfdPYSm3BZnC6t95FoFwFtM8br1VjfybmzvbXYHl5AobOO5CyNVarHQtUCCb2z7IntWqieT6dh9m3j2dfT8_zxZf5p9OTRa4JhUUuBCdQ1yXTvBZMaFxrhNHM1DWDFRaY0RKTmjOkFE-PmBGBMYWMFBUrqTL4MHs_-nZD2ZpKG9cH1cgu2FaFrfTKyj9_nL2Wa38rEeSYcpgMXk8GwX8fUnLZ2qhN0yhn_BAlKwgnjJIEvvoL3PghuLScLCAniCHCE4RHSAcfYzD1fRIE5a5LuetSTl3Kscukevn7Eg-aqbwE8BG4s43Z_o-nPPv8YUlxkaSzURqTyq1NeIj970j5KLOxNz_uJ6pwIylLNcjVxVyKq_liOYeXcoF_Acv31rg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>208517158</pqid></control><display><type>article</type><title>Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>PubMed Central</source><creator>Constantinou, Angelos ; Tarsounas, Madalena ; Karow, Julia K ; Brosh, Robert M ; Bohr, Vilhelm A ; Hickson, Ian D ; West, Stephen C</creator><creatorcontrib>Constantinou, Angelos ; Tarsounas, Madalena ; Karow, Julia K ; Brosh, Robert M ; Bohr, Vilhelm A ; Hickson, Ian D ; West, Stephen C</creatorcontrib><description>Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The
WRN
gene encodes a 3′–5′ DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (
BLM
). In this work, we show that WRN promotes the ATP‐dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S‐phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single‐stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>DOI: 10.1093/embo-reports/kvd004</identifier><identifier>PMID: 11256630</identifier><identifier>CODEN: ERMEAX</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adenosine Triphosphatases - genetics ; Adenosine Triphosphatases - metabolism ; Adenosine Triphosphate - metabolism ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Cell Nucleus - metabolism ; Deoxyribonucleic acid ; DNA ; DNA - genetics ; DNA - metabolism ; DNA Helicases - genetics ; DNA Helicases - metabolism ; DNA Replication ; Exodeoxyribonucleases ; HeLa Cells ; Humans ; Microscopy, Fluorescence ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Recombination, Genetic ; RecQ Helicases ; Scientific Report ; Scientific Reports ; Translocation ; Werner Syndrome - genetics ; Werner Syndrome - metabolism ; Werner Syndrome Helicase</subject><ispartof>EMBO reports, 2000-07, Vol.1 (1), p.80-84</ispartof><rights>European Molecular Biology Organization 2000</rights><rights>Copyright © 2000 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Jul 15, 2000</rights><rights>Copyright © 2000 European Molecular Biology Organization 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5602-99850cfb7c8f979c3fc1314eff70d39376b35f871aa8eff37593360752d7b6ae3</citedby><cites>FETCH-LOGICAL-c5602-99850cfb7c8f979c3fc1314eff70d39376b35f871aa8eff37593360752d7b6ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083680/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083680/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11256630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Constantinou, Angelos</creatorcontrib><creatorcontrib>Tarsounas, Madalena</creatorcontrib><creatorcontrib>Karow, Julia K</creatorcontrib><creatorcontrib>Brosh, Robert M</creatorcontrib><creatorcontrib>Bohr, Vilhelm A</creatorcontrib><creatorcontrib>Hickson, Ian D</creatorcontrib><creatorcontrib>West, Stephen C</creatorcontrib><title>Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><addtitle>EMBO Rep</addtitle><description>Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The
WRN
gene encodes a 3′–5′ DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (
BLM
). In this work, we show that WRN promotes the ATP‐dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S‐phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single‐stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.</description><subject>Adenosine Triphosphatases - genetics</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Cell Nucleus - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Helicases - genetics</subject><subject>DNA Helicases - metabolism</subject><subject>DNA Replication</subject><subject>Exodeoxyribonucleases</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Microscopy, Fluorescence</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombination, Genetic</subject><subject>RecQ Helicases</subject><subject>Scientific Report</subject><subject>Scientific Reports</subject><subject>Translocation</subject><subject>Werner Syndrome - genetics</subject><subject>Werner Syndrome - metabolism</subject><subject>Werner Syndrome Helicase</subject><issn>1469-221X</issn><issn>1469-3178</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkUtv1DAUhSMEog_4BUjIYkFhEWrH49cGqVRlijSUagSa7izHcaaeJnawk5bh1-NRohZYIFa27O-ce65Olr1A8B2CAh-btvR5MJ0PfTy-ua0gnD3K9tGMihwjxh9P96JAV3vZQYwbCCERjD_N9hAqCKUY7mftygRnwlEEceuq4FsDuuB7Yx14s1pevAWtXQfVmwjOfdPYSm3BZnC6t95FoFwFtM8br1VjfybmzvbXYHl5AobOO5CyNVarHQtUCCb2z7IntWqieT6dh9m3j2dfT8_zxZf5p9OTRa4JhUUuBCdQ1yXTvBZMaFxrhNHM1DWDFRaY0RKTmjOkFE-PmBGBMYWMFBUrqTL4MHs_-nZD2ZpKG9cH1cgu2FaFrfTKyj9_nL2Wa38rEeSYcpgMXk8GwX8fUnLZ2qhN0yhn_BAlKwgnjJIEvvoL3PghuLScLCAniCHCE4RHSAcfYzD1fRIE5a5LuetSTl3Kscukevn7Eg-aqbwE8BG4s43Z_o-nPPv8YUlxkaSzURqTyq1NeIj970j5KLOxNz_uJ6pwIylLNcjVxVyKq_liOYeXcoF_Acv31rg</recordid><startdate>200007</startdate><enddate>200007</enddate><creator>Constantinou, Angelos</creator><creator>Tarsounas, Madalena</creator><creator>Karow, Julia K</creator><creator>Brosh, Robert M</creator><creator>Bohr, Vilhelm A</creator><creator>Hickson, Ian D</creator><creator>West, Stephen C</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200007</creationdate><title>Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest</title><author>Constantinou, Angelos ; Tarsounas, Madalena ; Karow, Julia K ; Brosh, Robert M ; Bohr, Vilhelm A ; Hickson, Ian D ; West, Stephen C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5602-99850cfb7c8f979c3fc1314eff70d39376b35f871aa8eff37593360752d7b6ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenosine Triphosphatases - genetics</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Cell Nucleus - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA Helicases - genetics</topic><topic>DNA Helicases - metabolism</topic><topic>DNA Replication</topic><topic>Exodeoxyribonucleases</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Microscopy, Fluorescence</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombination, Genetic</topic><topic>RecQ Helicases</topic><topic>Scientific Report</topic><topic>Scientific Reports</topic><topic>Translocation</topic><topic>Werner Syndrome - genetics</topic><topic>Werner Syndrome - metabolism</topic><topic>Werner Syndrome Helicase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Constantinou, Angelos</creatorcontrib><creatorcontrib>Tarsounas, Madalena</creatorcontrib><creatorcontrib>Karow, Julia K</creatorcontrib><creatorcontrib>Brosh, Robert M</creatorcontrib><creatorcontrib>Bohr, Vilhelm A</creatorcontrib><creatorcontrib>Hickson, Ian D</creatorcontrib><creatorcontrib>West, Stephen C</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Constantinou, Angelos</au><au>Tarsounas, Madalena</au><au>Karow, Julia K</au><au>Brosh, Robert M</au><au>Bohr, Vilhelm A</au><au>Hickson, Ian D</au><au>West, Stephen C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest</atitle><jtitle>EMBO reports</jtitle><stitle>EMBO Rep</stitle><addtitle>EMBO Rep</addtitle><date>2000-07</date><risdate>2000</risdate><volume>1</volume><issue>1</issue><spage>80</spage><epage>84</epage><pages>80-84</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><coden>ERMEAX</coden><abstract>Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The
WRN
gene encodes a 3′–5′ DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (
BLM
). In this work, we show that WRN promotes the ATP‐dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S‐phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single‐stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>11256630</pmid><doi>10.1093/embo-reports/kvd004</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1469-221X |
| ispartof | EMBO reports, 2000-07, Vol.1 (1), p.80-84 |
| issn | 1469-221X 1469-3178 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1083680 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; PubMed Central |
| subjects | Adenosine Triphosphatases - genetics Adenosine Triphosphatases - metabolism Adenosine Triphosphate - metabolism Bacterial Proteins - genetics Bacterial Proteins - metabolism Cell Nucleus - metabolism Deoxyribonucleic acid DNA DNA - genetics DNA - metabolism DNA Helicases - genetics DNA Helicases - metabolism DNA Replication Exodeoxyribonucleases HeLa Cells Humans Microscopy, Fluorescence Recombinant Proteins - genetics Recombinant Proteins - metabolism Recombination, Genetic RecQ Helicases Scientific Report Scientific Reports Translocation Werner Syndrome - genetics Werner Syndrome - metabolism Werner Syndrome Helicase |
| title | Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T22%3A07%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Werner's%20syndrome%20protein%20(WRN)%20migrates%20Holliday%20junctions%20and%20co-localizes%20with%20RPA%20upon%20replication%20arrest&rft.jtitle=EMBO%20reports&rft.au=Constantinou,%20Angelos&rft.date=2000-07&rft.volume=1&rft.issue=1&rft.spage=80&rft.epage=84&rft.pages=80-84&rft.issn=1469-221X&rft.eissn=1469-3178&rft.coden=ERMEAX&rft_id=info:doi/10.1093/embo-reports/kvd004&rft_dat=%3Cproquest_pubme%3E373527301%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=208517158&rft_id=info:pmid/11256630&rfr_iscdi=true |