A small protein that mediates the activation of a two-component system by another two-component system
The PmrA–PmrB two‐component system of Salmonella enterica controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA‐activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a pr...
Gespeichert in:
Veröffentlicht in: | The EMBO journal 2000-04, Vol.19 (8), p.1861-1872 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1872 |
---|---|
container_issue | 8 |
container_start_page | 1861 |
container_title | The EMBO journal |
container_volume | 19 |
creator | Kox, Linda F.F. Wösten, Marc M.S.M. Groisman, Eduardo A. |
description | The PmrA–PmrB two‐component system of
Salmonella enterica
controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA‐activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two‐component system, PhoP–PhoQ. Here, we define the genetic basis for the interaction between the PhoP–PhoQ and PmrA–PmrB systems. We have identified
pmrD
as a PhoP‐activated gene that mediates the transcriptional activation of PmrA‐regulated genes during growth in low magnesium. When transcription of
pmrD
is driven from a heterologous promoter, expression of PmrA‐activated genes occurs even at repressing magnesium concentrations and becomes independent of the
phoP
and
phoQ
genes. The PmrD effect is specific for PmrA‐regulated genes and requires functional PmrA and PmrB proteins. A
pmrD
mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA–PmrB system at a post‐transcriptional level. |
doi_str_mv | 10.1093/emboj/19.8.1861 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_302009</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>374528061</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5962-d9d2cd64854d379a9e35776e20f37c1e3a2bebd00386c76d91c4e4b865e21473</originalsourceid><addsrcrecordid>eNqFkc9v0zAcxS0EYqVw5gSyOHBL6x-xnRw4jGoM0AAhJnG0HOfbLSWxi-1s9L_HW6ZSEIiTZb3P-_p9_RB6SsmCkpovYWj8ZknrRbWglaT30IyWkhSMKHEfzQiTtChpVR-hRzFuCCGiUvQhOqJEKcEUmaH1MY6D6Xu8DT5B53C6NAkP0HYmQcw3wMam7sqkzjvs19jgdO0L64etd-ASjruYYMDNDhvnMx7-qj9GD9amj_Dk7pyj8zcn56u3xdmn03er47PCilqyoq1bZltZVqJsuapNDVwoJYGRNVeWAjesgaYlhFfSKtnW1JZQNpUUwGip-By9msZuxybvYHOAYHq9Dd1gwk570-nfFddd6gt_pTlhJP_nHL288wf_fYSY9NBFC31vHPgxaqoEF7IsM_jiD3Djx-DyaprWgklVUZah5QTZ4GMMsN4HoUTf1Kdv68sOXemb-rLj-WH-A37qKwPVBFx3Pez-N0-ffHj9Xomak9s0ZLLG7HIXEA4i_zPOs8niTBoD7J_7NbKY9C53_GMvm_BNS8WV0F8_nmrKVquSfxH6M_8JCrrTHw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>195267812</pqid></control><display><type>article</type><title>A small protein that mediates the activation of a two-component system by another two-component system</title><source>MEDLINE</source><source>Wiley Online Library Free Content</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Kox, Linda F.F. ; Wösten, Marc M.S.M. ; Groisman, Eduardo A.</creator><creatorcontrib>Kox, Linda F.F. ; Wösten, Marc M.S.M. ; Groisman, Eduardo A.</creatorcontrib><description>The PmrA–PmrB two‐component system of
Salmonella enterica
controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA‐activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two‐component system, PhoP–PhoQ. Here, we define the genetic basis for the interaction between the PhoP–PhoQ and PmrA–PmrB systems. We have identified
pmrD
as a PhoP‐activated gene that mediates the transcriptional activation of PmrA‐regulated genes during growth in low magnesium. When transcription of
pmrD
is driven from a heterologous promoter, expression of PmrA‐activated genes occurs even at repressing magnesium concentrations and becomes independent of the
phoP
and
phoQ
genes. The PmrD effect is specific for PmrA‐regulated genes and requires functional PmrA and PmrB proteins. A
pmrD
mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA–PmrB system at a post‐transcriptional level.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/19.8.1861</identifier><identifier>PMID: 10775270</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Anti-Bacterial Agents - metabolism ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Base Sequence ; Drug Resistance, Microbial ; Iron - metabolism ; Magnesium ; Magnesium - metabolism ; Models, Biological ; Molecular Sequence Data ; Mutagenesis ; Mutation ; PhoP protein ; PhoP-PhoQ ; PhoQ protein ; Phosphorylation ; Plasmids ; PmrA protein ; PmrA-PmrB ; PmrB protein ; pmrD gene ; PmrD protein ; polymyxin ; Polymyxins - metabolism ; Protein Binding ; Recombinant Proteins - metabolism ; RNA Processing, Post-Transcriptional ; Salmonella enterica ; Salmonella enterica - chemistry ; Signal Transduction ; Single-Strand Specific DNA and RNA Endonucleases - metabolism ; transcription ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic</subject><ispartof>The EMBO journal, 2000-04, Vol.19 (8), p.1861-1872</ispartof><rights>European Molecular Biology Organization 2000</rights><rights>Copyright © 2000 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Apr 17, 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-c5962-d9d2cd64854d379a9e35776e20f37c1e3a2bebd00386c76d91c4e4b865e21473</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC302009/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC302009/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10775270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kox, Linda F.F.</creatorcontrib><creatorcontrib>Wösten, Marc M.S.M.</creatorcontrib><creatorcontrib>Groisman, Eduardo A.</creatorcontrib><title>A small protein that mediates the activation of a two-component system by another two-component system</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>The PmrA–PmrB two‐component system of
Salmonella enterica
controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA‐activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two‐component system, PhoP–PhoQ. Here, we define the genetic basis for the interaction between the PhoP–PhoQ and PmrA–PmrB systems. We have identified
pmrD
as a PhoP‐activated gene that mediates the transcriptional activation of PmrA‐regulated genes during growth in low magnesium. When transcription of
pmrD
is driven from a heterologous promoter, expression of PmrA‐activated genes occurs even at repressing magnesium concentrations and becomes independent of the
phoP
and
phoQ
genes. The PmrD effect is specific for PmrA‐regulated genes and requires functional PmrA and PmrB proteins. A
pmrD
mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA–PmrB system at a post‐transcriptional level.</description><subject>Anti-Bacterial Agents - metabolism</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Base Sequence</subject><subject>Drug Resistance, Microbial</subject><subject>Iron - metabolism</subject><subject>Magnesium</subject><subject>Magnesium - metabolism</subject><subject>Models, Biological</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis</subject><subject>Mutation</subject><subject>PhoP protein</subject><subject>PhoP-PhoQ</subject><subject>PhoQ protein</subject><subject>Phosphorylation</subject><subject>Plasmids</subject><subject>PmrA protein</subject><subject>PmrA-PmrB</subject><subject>PmrB protein</subject><subject>pmrD gene</subject><subject>PmrD protein</subject><subject>polymyxin</subject><subject>Polymyxins - metabolism</subject><subject>Protein Binding</subject><subject>Recombinant Proteins - metabolism</subject><subject>RNA Processing, Post-Transcriptional</subject><subject>Salmonella enterica</subject><subject>Salmonella enterica - chemistry</subject><subject>Signal Transduction</subject><subject>Single-Strand Specific DNA and RNA Endonucleases - metabolism</subject><subject>transcription</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</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>eNqFkc9v0zAcxS0EYqVw5gSyOHBL6x-xnRw4jGoM0AAhJnG0HOfbLSWxi-1s9L_HW6ZSEIiTZb3P-_p9_RB6SsmCkpovYWj8ZknrRbWglaT30IyWkhSMKHEfzQiTtChpVR-hRzFuCCGiUvQhOqJEKcEUmaH1MY6D6Xu8DT5B53C6NAkP0HYmQcw3wMam7sqkzjvs19jgdO0L64etd-ASjruYYMDNDhvnMx7-qj9GD9amj_Dk7pyj8zcn56u3xdmn03er47PCilqyoq1bZltZVqJsuapNDVwoJYGRNVeWAjesgaYlhFfSKtnW1JZQNpUUwGip-By9msZuxybvYHOAYHq9Dd1gwk570-nfFddd6gt_pTlhJP_nHL288wf_fYSY9NBFC31vHPgxaqoEF7IsM_jiD3Djx-DyaprWgklVUZah5QTZ4GMMsN4HoUTf1Kdv68sOXemb-rLj-WH-A37qKwPVBFx3Pez-N0-ffHj9Xomak9s0ZLLG7HIXEA4i_zPOs8niTBoD7J_7NbKY9C53_GMvm_BNS8WV0F8_nmrKVquSfxH6M_8JCrrTHw</recordid><startdate>20000417</startdate><enddate>20000417</enddate><creator>Kox, Linda F.F.</creator><creator>Wösten, Marc M.S.M.</creator><creator>Groisman, Eduardo A.</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</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>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</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>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20000417</creationdate><title>A small protein that mediates the activation of a two-component system by another two-component system</title><author>Kox, Linda F.F. ; Wösten, Marc M.S.M. ; Groisman, Eduardo A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5962-d9d2cd64854d379a9e35776e20f37c1e3a2bebd00386c76d91c4e4b865e21473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Anti-Bacterial Agents - metabolism</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Base Sequence</topic><topic>Drug Resistance, Microbial</topic><topic>Iron - metabolism</topic><topic>Magnesium</topic><topic>Magnesium - metabolism</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis</topic><topic>Mutation</topic><topic>PhoP protein</topic><topic>PhoP-PhoQ</topic><topic>PhoQ protein</topic><topic>Phosphorylation</topic><topic>Plasmids</topic><topic>PmrA protein</topic><topic>PmrA-PmrB</topic><topic>PmrB protein</topic><topic>pmrD gene</topic><topic>PmrD protein</topic><topic>polymyxin</topic><topic>Polymyxins - metabolism</topic><topic>Protein Binding</topic><topic>Recombinant Proteins - metabolism</topic><topic>RNA Processing, Post-Transcriptional</topic><topic>Salmonella enterica</topic><topic>Salmonella enterica - chemistry</topic><topic>Signal Transduction</topic><topic>Single-Strand Specific DNA and RNA Endonucleases - metabolism</topic><topic>transcription</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kox, Linda F.F.</creatorcontrib><creatorcontrib>Wösten, Marc M.S.M.</creatorcontrib><creatorcontrib>Groisman, Eduardo A.</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences 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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic 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>Earth, Atmospheric & Aquatic Science Database</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>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kox, Linda F.F.</au><au>Wösten, Marc M.S.M.</au><au>Groisman, Eduardo A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A small protein that mediates the activation of a two-component system by another two-component system</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2000-04-17</date><risdate>2000</risdate><volume>19</volume><issue>8</issue><spage>1861</spage><epage>1872</epage><pages>1861-1872</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>The PmrA–PmrB two‐component system of
Salmonella enterica
controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA‐activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two‐component system, PhoP–PhoQ. Here, we define the genetic basis for the interaction between the PhoP–PhoQ and PmrA–PmrB systems. We have identified
pmrD
as a PhoP‐activated gene that mediates the transcriptional activation of PmrA‐regulated genes during growth in low magnesium. When transcription of
pmrD
is driven from a heterologous promoter, expression of PmrA‐activated genes occurs even at repressing magnesium concentrations and becomes independent of the
phoP
and
phoQ
genes. The PmrD effect is specific for PmrA‐regulated genes and requires functional PmrA and PmrB proteins. A
pmrD
mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA–PmrB system at a post‐transcriptional level.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>10775270</pmid><doi>10.1093/emboj/19.8.1861</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0261-4189 |
ispartof | The EMBO journal, 2000-04, Vol.19 (8), p.1861-1872 |
issn | 0261-4189 1460-2075 1460-2075 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_302009 |
source | MEDLINE; Wiley Online Library Free Content; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Anti-Bacterial Agents - metabolism Bacterial Proteins - genetics Bacterial Proteins - metabolism Base Sequence Drug Resistance, Microbial Iron - metabolism Magnesium Magnesium - metabolism Models, Biological Molecular Sequence Data Mutagenesis Mutation PhoP protein PhoP-PhoQ PhoQ protein Phosphorylation Plasmids PmrA protein PmrA-PmrB PmrB protein pmrD gene PmrD protein polymyxin Polymyxins - metabolism Protein Binding Recombinant Proteins - metabolism RNA Processing, Post-Transcriptional Salmonella enterica Salmonella enterica - chemistry Signal Transduction Single-Strand Specific DNA and RNA Endonucleases - metabolism transcription Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
title | A small protein that mediates the activation of a two-component system by another two-component system |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T13%3A18%3A23IST&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=A%20small%20protein%20that%20mediates%20the%20activation%20of%20a%20two-component%20system%20by%20another%20two-component%20system&rft.jtitle=The%20EMBO%20journal&rft.au=Kox,%20Linda%20F.F.&rft.date=2000-04-17&rft.volume=19&rft.issue=8&rft.spage=1861&rft.epage=1872&rft.pages=1861-1872&rft.issn=0261-4189&rft.eissn=1460-2075&rft.coden=EMJODG&rft_id=info:doi/10.1093/emboj/19.8.1861&rft_dat=%3Cproquest_pubme%3E374528061%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=195267812&rft_id=info:pmid/10775270&rfr_iscdi=true |