Plant MCM proteins: role in DNA replication and beyond

Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2–7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Plant molecular biology 2011-12, Vol.77 (6), p.537-545
Hauptverfasser: Tuteja, Narendra, Tran, Ngoc Quang, Dang, Hung Quang, Tuteja, Renu
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 545
container_issue 6
container_start_page 537
container_title Plant molecular biology
container_volume 77
creator Tuteja, Narendra
Tran, Ngoc Quang
Dang, Hung Quang
Tuteja, Renu
description Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2–7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role in plasmid replication or cell cycle progression. Each of six MCM contains highly conserved sequence called “MCM box”, which contains two ATPase consensus Walker A and Walker B motifs. Studies on MCM proteins showed that (a) the replication origins are licensed by stable binding of MCM2–7 to form pre-RC (pre-replicative complex) during G1 phase of the cell cycle, (b) the activation of MCM proteins by CDKs (cyclin-dependent kinases) and DDKs (Dbf4-dependent kinases) and their helicase activity are important for pre-RC to initiate the DNA replication, and (c) the release of MCMs from chromatin renders the origins “unlicensed”. DNA replication licensing in plant is, in general, less characterized. The MCMs have been reported from Arabidopsis, maize, tobacco, pea and rice, where they are found to be highly expressed in dividing tissues such as shoot apex and root tips, localized in nucleus and cytosol and play important role in DNA replication, megagametophyte and embryo development. The identification of six MCM coding genes from pea and Arabidopsis suggest six distinct classes of MCM protein in higher plant, and the conserved function right across the eukaryotes. This overview of MCMs contains an emphasis on MCMs from plants and the novel role of MCM6 in abiotic stress tolerance.
doi_str_mv 10.1007/s11103-011-9836-3
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_904218995</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2511274521</sourcerecordid><originalsourceid>FETCH-LOGICAL-c403t-31d7d5db09474ebc0a70ec7bec56287f1fa629d7fc74ad9a9bc6cd5635196cf23</originalsourceid><addsrcrecordid>eNp9kL1OwzAURi0EoqXwACzIYoHFcG0ndsxWlV-pBQaYI8d2UFCaFDsZ-va4SgEJCSYP93zH934IHVO4oADyMlBKgROglKiMC8J30JimkpMUWLaLxkCFJElC2QgdhPAOEFNc7KMRY8AzUHyMxHOtmw4vZgu88m3nqiZcYd_WDlcNvn6cYu9WdWV0V7UN1o3FhVu3jT1Ee6WugzvavhP0envzMrsn86e7h9l0TkwCvCOcWmlTW4BKZOIKA1qCM7JwJhUskyUttWDKytLIRFulVWGEsangKVXClIxP0Nngjct99C50-bIKxtVxadf2IVeQMJoplUby_F8ynp5lPAXYSE9_oe9t75t4R_RxBZLG5SeIDpDxbQjelfnKV0vt19G0kcl8aD-P7eeb9nMeMydbcV8snf1OfNUdATYAIY6aN-d_fv7b-gmHroyQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>903907140</pqid></control><display><type>article</type><title>Plant MCM proteins: role in DNA replication and beyond</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Tuteja, Narendra ; Tran, Ngoc Quang ; Dang, Hung Quang ; Tuteja, Renu</creator><creatorcontrib>Tuteja, Narendra ; Tran, Ngoc Quang ; Dang, Hung Quang ; Tuteja, Renu</creatorcontrib><description>Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2–7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role in plasmid replication or cell cycle progression. Each of six MCM contains highly conserved sequence called “MCM box”, which contains two ATPase consensus Walker A and Walker B motifs. Studies on MCM proteins showed that (a) the replication origins are licensed by stable binding of MCM2–7 to form pre-RC (pre-replicative complex) during G1 phase of the cell cycle, (b) the activation of MCM proteins by CDKs (cyclin-dependent kinases) and DDKs (Dbf4-dependent kinases) and their helicase activity are important for pre-RC to initiate the DNA replication, and (c) the release of MCMs from chromatin renders the origins “unlicensed”. DNA replication licensing in plant is, in general, less characterized. The MCMs have been reported from Arabidopsis, maize, tobacco, pea and rice, where they are found to be highly expressed in dividing tissues such as shoot apex and root tips, localized in nucleus and cytosol and play important role in DNA replication, megagametophyte and embryo development. The identification of six MCM coding genes from pea and Arabidopsis suggest six distinct classes of MCM protein in higher plant, and the conserved function right across the eukaryotes. This overview of MCMs contains an emphasis on MCMs from plants and the novel role of MCM6 in abiotic stress tolerance.</description><identifier>ISSN: 0167-4412</identifier><identifier>EISSN: 1573-5028</identifier><identifier>DOI: 10.1007/s11103-011-9836-3</identifier><identifier>PMID: 22038093</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adenosinetriphosphatase ; Arabidopsis ; Biochemistry ; Biomedical and Life Sciences ; Cell cycle ; Cell Cycle - genetics ; Cell Cycle - physiology ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Chromatin ; Chromosomes ; Conserved sequence ; Cyclin-dependent kinase ; Cytosol ; Deoxyribonucleic acid ; Development ; DNA ; DNA biosynthesis ; DNA helicase ; DNA Replication - genetics ; DNA Replication - physiology ; Embryos ; Flowers &amp; plants ; G1 phase ; genomics ; Licensing ; Life Sciences ; MCM protein ; Nuclei ; Oryza sativa ; Plant biology ; Plant Pathology ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Plant Sciences ; Plasmids ; Proteins ; Replication ; Replication origins ; Review ; Reviews ; Roots ; S phase ; Shoots ; Stress ; Tobacco ; Yeasts ; Zea mays</subject><ispartof>Plant molecular biology, 2011-12, Vol.77 (6), p.537-545</ispartof><rights>Springer Science+Business Media B.V. 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-31d7d5db09474ebc0a70ec7bec56287f1fa629d7fc74ad9a9bc6cd5635196cf23</citedby><cites>FETCH-LOGICAL-c403t-31d7d5db09474ebc0a70ec7bec56287f1fa629d7fc74ad9a9bc6cd5635196cf23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11103-011-9836-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11103-011-9836-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22038093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tuteja, Narendra</creatorcontrib><creatorcontrib>Tran, Ngoc Quang</creatorcontrib><creatorcontrib>Dang, Hung Quang</creatorcontrib><creatorcontrib>Tuteja, Renu</creatorcontrib><title>Plant MCM proteins: role in DNA replication and beyond</title><title>Plant molecular biology</title><addtitle>Plant Mol Biol</addtitle><addtitle>Plant Mol Biol</addtitle><description>Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2–7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role in plasmid replication or cell cycle progression. Each of six MCM contains highly conserved sequence called “MCM box”, which contains two ATPase consensus Walker A and Walker B motifs. Studies on MCM proteins showed that (a) the replication origins are licensed by stable binding of MCM2–7 to form pre-RC (pre-replicative complex) during G1 phase of the cell cycle, (b) the activation of MCM proteins by CDKs (cyclin-dependent kinases) and DDKs (Dbf4-dependent kinases) and their helicase activity are important for pre-RC to initiate the DNA replication, and (c) the release of MCMs from chromatin renders the origins “unlicensed”. DNA replication licensing in plant is, in general, less characterized. The MCMs have been reported from Arabidopsis, maize, tobacco, pea and rice, where they are found to be highly expressed in dividing tissues such as shoot apex and root tips, localized in nucleus and cytosol and play important role in DNA replication, megagametophyte and embryo development. The identification of six MCM coding genes from pea and Arabidopsis suggest six distinct classes of MCM protein in higher plant, and the conserved function right across the eukaryotes. This overview of MCMs contains an emphasis on MCMs from plants and the novel role of MCM6 in abiotic stress tolerance.</description><subject>Adenosinetriphosphatase</subject><subject>Arabidopsis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle - physiology</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Chromatin</subject><subject>Chromosomes</subject><subject>Conserved sequence</subject><subject>Cyclin-dependent kinase</subject><subject>Cytosol</subject><subject>Deoxyribonucleic acid</subject><subject>Development</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA helicase</subject><subject>DNA Replication - genetics</subject><subject>DNA Replication - physiology</subject><subject>Embryos</subject><subject>Flowers &amp; plants</subject><subject>G1 phase</subject><subject>genomics</subject><subject>Licensing</subject><subject>Life Sciences</subject><subject>MCM protein</subject><subject>Nuclei</subject><subject>Oryza sativa</subject><subject>Plant biology</subject><subject>Plant Pathology</subject><subject>Plant Proteins - genetics</subject><subject>Plant Proteins - metabolism</subject><subject>Plant Sciences</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Replication</subject><subject>Replication origins</subject><subject>Review</subject><subject>Reviews</subject><subject>Roots</subject><subject>S phase</subject><subject>Shoots</subject><subject>Stress</subject><subject>Tobacco</subject><subject>Yeasts</subject><subject>Zea mays</subject><issn>0167-4412</issn><issn>1573-5028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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>eNp9kL1OwzAURi0EoqXwACzIYoHFcG0ndsxWlV-pBQaYI8d2UFCaFDsZ-va4SgEJCSYP93zH934IHVO4oADyMlBKgROglKiMC8J30JimkpMUWLaLxkCFJElC2QgdhPAOEFNc7KMRY8AzUHyMxHOtmw4vZgu88m3nqiZcYd_WDlcNvn6cYu9WdWV0V7UN1o3FhVu3jT1Ee6WugzvavhP0envzMrsn86e7h9l0TkwCvCOcWmlTW4BKZOIKA1qCM7JwJhUskyUttWDKytLIRFulVWGEsangKVXClIxP0Nngjct99C50-bIKxtVxadf2IVeQMJoplUby_F8ynp5lPAXYSE9_oe9t75t4R_RxBZLG5SeIDpDxbQjelfnKV0vt19G0kcl8aD-P7eeb9nMeMydbcV8snf1OfNUdATYAIY6aN-d_fv7b-gmHroyQ</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Tuteja, Narendra</creator><creator>Tran, Ngoc Quang</creator><creator>Dang, Hung Quang</creator><creator>Tuteja, Renu</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><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>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</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></search><sort><creationdate>20111201</creationdate><title>Plant MCM proteins: role in DNA replication and beyond</title><author>Tuteja, Narendra ; Tran, Ngoc Quang ; Dang, Hung Quang ; Tuteja, Renu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-31d7d5db09474ebc0a70ec7bec56287f1fa629d7fc74ad9a9bc6cd5635196cf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenosinetriphosphatase</topic><topic>Arabidopsis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Cycle - physiology</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Chromatin</topic><topic>Chromosomes</topic><topic>Conserved sequence</topic><topic>Cyclin-dependent kinase</topic><topic>Cytosol</topic><topic>Deoxyribonucleic acid</topic><topic>Development</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA helicase</topic><topic>DNA Replication - genetics</topic><topic>DNA Replication - physiology</topic><topic>Embryos</topic><topic>Flowers &amp; plants</topic><topic>G1 phase</topic><topic>genomics</topic><topic>Licensing</topic><topic>Life Sciences</topic><topic>MCM protein</topic><topic>Nuclei</topic><topic>Oryza sativa</topic><topic>Plant biology</topic><topic>Plant Pathology</topic><topic>Plant Proteins - genetics</topic><topic>Plant Proteins - metabolism</topic><topic>Plant Sciences</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Replication</topic><topic>Replication origins</topic><topic>Review</topic><topic>Reviews</topic><topic>Roots</topic><topic>S phase</topic><topic>Shoots</topic><topic>Stress</topic><topic>Tobacco</topic><topic>Yeasts</topic><topic>Zea mays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tuteja, Narendra</creatorcontrib><creatorcontrib>Tran, Ngoc Quang</creatorcontrib><creatorcontrib>Dang, Hung Quang</creatorcontrib><creatorcontrib>Tuteja, Renu</creatorcontrib><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>Nucleic Acids Abstracts</collection><collection>Health &amp; 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>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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</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><jtitle>Plant molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tuteja, Narendra</au><au>Tran, Ngoc Quang</au><au>Dang, Hung Quang</au><au>Tuteja, Renu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plant MCM proteins: role in DNA replication and beyond</atitle><jtitle>Plant molecular biology</jtitle><stitle>Plant Mol Biol</stitle><addtitle>Plant Mol Biol</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>77</volume><issue>6</issue><spage>537</spage><epage>545</epage><pages>537-545</pages><issn>0167-4412</issn><eissn>1573-5028</eissn><abstract>Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2–7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role in plasmid replication or cell cycle progression. Each of six MCM contains highly conserved sequence called “MCM box”, which contains two ATPase consensus Walker A and Walker B motifs. Studies on MCM proteins showed that (a) the replication origins are licensed by stable binding of MCM2–7 to form pre-RC (pre-replicative complex) during G1 phase of the cell cycle, (b) the activation of MCM proteins by CDKs (cyclin-dependent kinases) and DDKs (Dbf4-dependent kinases) and their helicase activity are important for pre-RC to initiate the DNA replication, and (c) the release of MCMs from chromatin renders the origins “unlicensed”. DNA replication licensing in plant is, in general, less characterized. The MCMs have been reported from Arabidopsis, maize, tobacco, pea and rice, where they are found to be highly expressed in dividing tissues such as shoot apex and root tips, localized in nucleus and cytosol and play important role in DNA replication, megagametophyte and embryo development. The identification of six MCM coding genes from pea and Arabidopsis suggest six distinct classes of MCM protein in higher plant, and the conserved function right across the eukaryotes. This overview of MCMs contains an emphasis on MCMs from plants and the novel role of MCM6 in abiotic stress tolerance.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>22038093</pmid><doi>10.1007/s11103-011-9836-3</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0167-4412
ispartof Plant molecular biology, 2011-12, Vol.77 (6), p.537-545
issn 0167-4412
1573-5028
language eng
recordid cdi_proquest_miscellaneous_904218995
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Adenosinetriphosphatase
Arabidopsis
Biochemistry
Biomedical and Life Sciences
Cell cycle
Cell Cycle - genetics
Cell Cycle - physiology
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Chromatin
Chromosomes
Conserved sequence
Cyclin-dependent kinase
Cytosol
Deoxyribonucleic acid
Development
DNA
DNA biosynthesis
DNA helicase
DNA Replication - genetics
DNA Replication - physiology
Embryos
Flowers & plants
G1 phase
genomics
Licensing
Life Sciences
MCM protein
Nuclei
Oryza sativa
Plant biology
Plant Pathology
Plant Proteins - genetics
Plant Proteins - metabolism
Plant Sciences
Plasmids
Proteins
Replication
Replication origins
Review
Reviews
Roots
S phase
Shoots
Stress
Tobacco
Yeasts
Zea mays
title Plant MCM proteins: role in DNA replication and beyond
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T14%3A36%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plant%20MCM%20proteins:%20role%20in%20DNA%20replication%20and%20beyond&rft.jtitle=Plant%20molecular%20biology&rft.au=Tuteja,%20Narendra&rft.date=2011-12-01&rft.volume=77&rft.issue=6&rft.spage=537&rft.epage=545&rft.pages=537-545&rft.issn=0167-4412&rft.eissn=1573-5028&rft_id=info:doi/10.1007/s11103-011-9836-3&rft_dat=%3Cproquest_cross%3E2511274521%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=903907140&rft_id=info:pmid/22038093&rfr_iscdi=true