BLM unfolds G-quadruplexes in different structural environments through different mechanisms
Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets fo...
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| Veröffentlicht in: | Nucleic acids research 2015-05, Vol.43 (9), p.4614-4626 |
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| creator | Wu, Wen-Qiang Hou, Xi-Miao Li, Ming Dou, Shuo-Xing Xi, Xu-Guang |
| description | Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms. |
| doi_str_mv | 10.1093/nar/gkv361 |
| format | Article |
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BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkv361</identifier><identifier>PMID: 25897130</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adenosine Triphosphate - metabolism ; DNA - chemistry ; DNA - metabolism ; DNA, Single-Stranded - metabolism ; Fluorescence Resonance Energy Transfer ; G-Quadruplexes ; Life Sciences ; Nucleic Acid Enzymes ; RecQ Helicases - metabolism</subject><ispartof>Nucleic acids research, 2015-05, Vol.43 (9), p.4614-4626</ispartof><rights>The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-defb645db03e48b08e1606f9b5b302f61112ec8524ec1c52b6de0dcda54854a23</citedby><cites>FETCH-LOGICAL-c445t-defb645db03e48b08e1606f9b5b302f61112ec8524ec1c52b6de0dcda54854a23</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/PMC4482088/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482088/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25897130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02396489$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Wen-Qiang</creatorcontrib><creatorcontrib>Hou, Xi-Miao</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Dou, Shuo-Xing</creatorcontrib><creatorcontrib>Xi, Xu-Guang</creatorcontrib><title>BLM unfolds G-quadruplexes in different structural environments through different mechanisms</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA, Single-Stranded - metabolism</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>G-Quadruplexes</subject><subject>Life Sciences</subject><subject>Nucleic Acid Enzymes</subject><subject>RecQ Helicases - metabolism</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS1ERbeFCx8A5QiV0nr8L84FqVTQVlrEBW5IlmNPNoHE2drxCr59s9pSFS6cRpr5zZs3eoS8BnoOtOYXwcaLzc8dV_CMrIArVopasedkRTmVJVChj8lJSj8oBQFSvCDHTOq6Ak5X5PuH9ecih3YafCquy7tsfczbAX9hKvpQ-L5tMWKYizTH7OYc7VBg2PVxCuPSTsXcxSlvuifkiK6zoU9jekmOWjskfPVQT8m3Tx-_Xt2U6y_Xt1eX69IJIefSY9soIX1DOQrdUI2gqGrrRjacslYBAEOnJRPowEnWKI_UO2-l0FJYxk_J-4PuNjcjere4WHyabexHG3-byfbm70noO7OZdkYIzajWi8C7g0D3z9rN5drse5TxWgld72Bh3z4ci9NdxjSbsU8Oh8EGnHIyUAGrKrbg_0eVZoJVTO9Vzw6oi1NKEdtHG0DNPmWzpGwOKS_wm6f_PqJ_YuX3Zm2lwg</recordid><startdate>20150519</startdate><enddate>20150519</enddate><creator>Wu, Wen-Qiang</creator><creator>Hou, Xi-Miao</creator><creator>Li, Ming</creator><creator>Dou, Shuo-Xing</creator><creator>Xi, Xu-Guang</creator><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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>1XC</scope><scope>5PM</scope></search><sort><creationdate>20150519</creationdate><title>BLM unfolds G-quadruplexes in different structural environments through different mechanisms</title><author>Wu, Wen-Qiang ; Hou, Xi-Miao ; Li, Ming ; Dou, Shuo-Xing ; Xi, Xu-Guang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-defb645db03e48b08e1606f9b5b302f61112ec8524ec1c52b6de0dcda54854a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>DNA, Single-Stranded - metabolism</topic><topic>Fluorescence Resonance Energy Transfer</topic><topic>G-Quadruplexes</topic><topic>Life Sciences</topic><topic>Nucleic Acid Enzymes</topic><topic>RecQ Helicases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Wen-Qiang</creatorcontrib><creatorcontrib>Hou, Xi-Miao</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Dou, Shuo-Xing</creatorcontrib><creatorcontrib>Xi, Xu-Guang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</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>Wu, Wen-Qiang</au><au>Hou, Xi-Miao</au><au>Li, Ming</au><au>Dou, Shuo-Xing</au><au>Xi, Xu-Guang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BLM unfolds G-quadruplexes in different structural environments through different mechanisms</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2015-05-19</date><risdate>2015</risdate><volume>43</volume><issue>9</issue><spage>4614</spage><epage>4626</epage><pages>4614-4626</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>25897130</pmid><doi>10.1093/nar/gkv361</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Oxford University Press (Open Access Collection); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenosine Triphosphate - metabolism DNA - chemistry DNA - metabolism DNA, Single-Stranded - metabolism Fluorescence Resonance Energy Transfer G-Quadruplexes Life Sciences Nucleic Acid Enzymes RecQ Helicases - metabolism |
| title | BLM unfolds G-quadruplexes in different structural environments through different mechanisms |
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