A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA
Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease activities. Our laboratory has recently unc...
Gespeichert in:
| Veröffentlicht in: | Nucleic acids research 2001-05, Vol.29 (9), p.1926-1934 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1934 |
|---|---|
| container_issue | 9 |
| container_start_page | 1926 |
| container_title | Nucleic acids research |
| container_volume | 29 |
| creator | Orren, D K Machwe, A Karmakar, P Piotrowski, J Cooper, M P Bohr, V A |
| description | Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments. |
| doi_str_mv | 10.1093/nar/29.9.1926 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_37248</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71321982</sourcerecordid><originalsourceid>FETCH-LOGICAL-c439t-4833e6b0e7d4bc583f614418ce1a268189e6f572b5bb425bf5e91556dfc6f1103</originalsourceid><addsrcrecordid>eNqFkbtvFDEQhy0EIuGgpEUWBd1ePH6tLdGcQniICBoQBYXl9Y4vjva8wd6F8N-zRw4INFQzo_nm-SPkMbA1MCtOsi8n3K7tGizXd8gxCM0baTW_e8s_Ig9qvWQMJCh5nxwBCG5Mq4_J5w2Ncw5TGrMfaMoTFv8zomOkb2f6LU0X9BOWjIXi9ZjnMKCvSKMPaUiTn7DSPm2x_qrp_c5vsacv3m0eknvRDxUfHeyKfHx59uH0dXP-_tWb0815E6SwUyONEKg7hm0vu6CMiBqkBBMQPNcGjEUdVcs71XWSqy4qtKCU7mPQEYCJFXl-0_dq7nbYB8xT8YO7Kmnny3c3-uT-zuR04bbjVydavgxfkWeH8jJ-mZdL3C7VgMPgM45zde3yLLCG_xcEsyzD-L7j03_Ay3Euy4Or44ypFqQQC9TcQKGMtRaMvxcG5vbSukVax62zbi_twj-5feUf-qCl-AHaeaAp</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>200571433</pqid></control><display><type>article</type><title>A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA</title><source>Oxford Journals Open Access Collection</source><source>MEDLINE</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Orren, D K ; Machwe, A ; Karmakar, P ; Piotrowski, J ; Cooper, M P ; Bohr, V A</creator><creatorcontrib>Orren, D K ; Machwe, A ; Karmakar, P ; Piotrowski, J ; Cooper, M P ; Bohr, V A</creatorcontrib><description>Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments.</description><identifier>ISSN: 1362-4962</identifier><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/29.9.1926</identifier><identifier>PMID: 11328876</identifier><identifier>CODEN: NARHAD</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Adenine - analogs & derivatives ; Adenine - chemistry ; Antigens, Nuclear ; Cell Line ; Cell Nucleus - chemistry ; DNA - chemistry ; DNA - metabolism ; DNA Damage ; DNA Helicases - analysis ; DNA Helicases - metabolism ; DNA Helicases - physiology ; DNA-Binding Proteins - analysis ; DNA-Binding Proteins - metabolism ; DNA-Binding Proteins - pharmacology ; DNA-Binding Proteins - physiology ; Exodeoxyribonucleases ; Exonucleases - analysis ; Exonucleases - metabolism ; Exonucleases - physiology ; Guanine - analogs & derivatives ; Guanine - chemistry ; HeLa Cells ; Humans ; Ku antigen ; Ku Autoantigen ; Nuclear Proteins - analysis ; Nuclear Proteins - metabolism ; Nuclear Proteins - physiology ; RecQ Helicases ; Replication Protein A ; V(D)J recombination ; Werner exonuclease ; Werner Syndrome Helicase</subject><ispartof>Nucleic acids research, 2001-05, Vol.29 (9), p.1926-1934</ispartof><rights>Copyright Oxford University Press(England) May 1, 2001</rights><rights>Copyright © 2001 Oxford University Press 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-4833e6b0e7d4bc583f614418ce1a268189e6f572b5bb425bf5e91556dfc6f1103</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/PMC37248/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC37248/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11328876$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orren, D K</creatorcontrib><creatorcontrib>Machwe, A</creatorcontrib><creatorcontrib>Karmakar, P</creatorcontrib><creatorcontrib>Piotrowski, J</creatorcontrib><creatorcontrib>Cooper, M P</creatorcontrib><creatorcontrib>Bohr, V A</creatorcontrib><title>A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments.</description><subject>Adenine - analogs & derivatives</subject><subject>Adenine - chemistry</subject><subject>Antigens, Nuclear</subject><subject>Cell Line</subject><subject>Cell Nucleus - chemistry</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA Damage</subject><subject>DNA Helicases - analysis</subject><subject>DNA Helicases - metabolism</subject><subject>DNA Helicases - physiology</subject><subject>DNA-Binding Proteins - analysis</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-Binding Proteins - pharmacology</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Exodeoxyribonucleases</subject><subject>Exonucleases - analysis</subject><subject>Exonucleases - metabolism</subject><subject>Exonucleases - physiology</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - chemistry</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Ku antigen</subject><subject>Ku Autoantigen</subject><subject>Nuclear Proteins - analysis</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Proteins - physiology</subject><subject>RecQ Helicases</subject><subject>Replication Protein A</subject><subject>V(D)J recombination</subject><subject>Werner exonuclease</subject><subject>Werner Syndrome Helicase</subject><issn>1362-4962</issn><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbtvFDEQhy0EIuGgpEUWBd1ePH6tLdGcQniICBoQBYXl9Y4vjva8wd6F8N-zRw4INFQzo_nm-SPkMbA1MCtOsi8n3K7tGizXd8gxCM0baTW_e8s_Ig9qvWQMJCh5nxwBCG5Mq4_J5w2Ncw5TGrMfaMoTFv8zomOkb2f6LU0X9BOWjIXi9ZjnMKCvSKMPaUiTn7DSPm2x_qrp_c5vsacv3m0eknvRDxUfHeyKfHx59uH0dXP-_tWb0815E6SwUyONEKg7hm0vu6CMiBqkBBMQPNcGjEUdVcs71XWSqy4qtKCU7mPQEYCJFXl-0_dq7nbYB8xT8YO7Kmnny3c3-uT-zuR04bbjVydavgxfkWeH8jJ-mZdL3C7VgMPgM45zde3yLLCG_xcEsyzD-L7j03_Ay3Euy4Or44ypFqQQC9TcQKGMtRaMvxcG5vbSukVax62zbi_twj-5feUf-qCl-AHaeaAp</recordid><startdate>20010501</startdate><enddate>20010501</enddate><creator>Orren, D K</creator><creator>Machwe, A</creator><creator>Karmakar, P</creator><creator>Piotrowski, J</creator><creator>Cooper, M P</creator><creator>Bohr, V A</creator><general>Oxford Publishing Limited (England)</general><general>Oxford University Press</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>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20010501</creationdate><title>A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA</title><author>Orren, D K ; Machwe, A ; Karmakar, P ; Piotrowski, J ; Cooper, M P ; Bohr, V A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-4833e6b0e7d4bc583f614418ce1a268189e6f572b5bb425bf5e91556dfc6f1103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adenine - analogs & derivatives</topic><topic>Adenine - chemistry</topic><topic>Antigens, Nuclear</topic><topic>Cell Line</topic><topic>Cell Nucleus - chemistry</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>DNA Damage</topic><topic>DNA Helicases - analysis</topic><topic>DNA Helicases - metabolism</topic><topic>DNA Helicases - physiology</topic><topic>DNA-Binding Proteins - analysis</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-Binding Proteins - pharmacology</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Exodeoxyribonucleases</topic><topic>Exonucleases - analysis</topic><topic>Exonucleases - metabolism</topic><topic>Exonucleases - physiology</topic><topic>Guanine - analogs & derivatives</topic><topic>Guanine - chemistry</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Ku antigen</topic><topic>Ku Autoantigen</topic><topic>Nuclear Proteins - analysis</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Proteins - physiology</topic><topic>RecQ Helicases</topic><topic>Replication Protein A</topic><topic>V(D)J recombination</topic><topic>Werner exonuclease</topic><topic>Werner Syndrome Helicase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orren, D K</creatorcontrib><creatorcontrib>Machwe, A</creatorcontrib><creatorcontrib>Karmakar, P</creatorcontrib><creatorcontrib>Piotrowski, J</creatorcontrib><creatorcontrib>Cooper, M P</creatorcontrib><creatorcontrib>Bohr, V A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orren, D K</au><au>Machwe, A</au><au>Karmakar, P</au><au>Piotrowski, J</au><au>Cooper, M P</au><au>Bohr, V A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>29</volume><issue>9</issue><spage>1926</spage><epage>1934</epage><pages>1926-1934</pages><issn>1362-4962</issn><issn>0305-1048</issn><eissn>1362-4962</eissn><coden>NARHAD</coden><abstract>Werner syndrome (WS) is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3'-->5' exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>11328876</pmid><doi>10.1093/nar/29.9.1926</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1362-4962 |
| ispartof | Nucleic acids research, 2001-05, Vol.29 (9), p.1926-1934 |
| issn | 1362-4962 0305-1048 1362-4962 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_37248 |
| source | Oxford Journals Open Access Collection; MEDLINE; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenine - analogs & derivatives Adenine - chemistry Antigens, Nuclear Cell Line Cell Nucleus - chemistry DNA - chemistry DNA - metabolism DNA Damage DNA Helicases - analysis DNA Helicases - metabolism DNA Helicases - physiology DNA-Binding Proteins - analysis DNA-Binding Proteins - metabolism DNA-Binding Proteins - pharmacology DNA-Binding Proteins - physiology Exodeoxyribonucleases Exonucleases - analysis Exonucleases - metabolism Exonucleases - physiology Guanine - analogs & derivatives Guanine - chemistry HeLa Cells Humans Ku antigen Ku Autoantigen Nuclear Proteins - analysis Nuclear Proteins - metabolism Nuclear Proteins - physiology RecQ Helicases Replication Protein A V(D)J recombination Werner exonuclease Werner Syndrome Helicase |
| title | A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T06%3A43%3A14IST&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%20functional%20interaction%20of%20Ku%20with%20Werner%20exonuclease%20facilitates%20digestion%20of%20damaged%20DNA&rft.jtitle=Nucleic%20acids%20research&rft.au=Orren,%20D%20K&rft.date=2001-05-01&rft.volume=29&rft.issue=9&rft.spage=1926&rft.epage=1934&rft.pages=1926-1934&rft.issn=1362-4962&rft.eissn=1362-4962&rft.coden=NARHAD&rft_id=info:doi/10.1093/nar/29.9.1926&rft_dat=%3Cproquest_pubme%3E71321982%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=200571433&rft_id=info:pmid/11328876&rfr_iscdi=true |