BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation
Bloom syndrome (BS) is a rare genetic disorder characterized by genomic instability and a high predisposition to cancer. The gene defective in BS, BLM , encodes a member of the RecQ family of 3′–5′ DNA helicases, and is proposed to function in recombinational repair during DNA replication. Here, we...
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| creator | Yodh, Jaya G Stevens, Benjamin C Kanagaraj, Radhakrishnan Janscak, Pavel Ha, Taekjip |
| description | Bloom syndrome (BS) is a rare genetic disorder characterized by genomic instability and a high predisposition to cancer. The gene defective in BS,
BLM
, encodes a member of the RecQ family of 3′–5′ DNA helicases, and is proposed to function in recombinational repair during DNA replication. Here, we have utilized single‐molecule fluorescence resonance energy transfer microscopy to examine the behaviour of BLM on forked DNA substrates. Strikingly, BLM unwound individual DNA molecules in a repetitive manner, unwinding a short length of duplex DNA followed by rapid reannealing and reinitiation of unwinding in several successions. Our results show that a monomeric BLM can ‘measure’ how many base pairs it has unwound, and once it has unwound a critical length, it reverses the unwinding reaction through strand switching and translocating on the opposing strand. Repetitive unwinding persisted even in the presence of hRPA, and interaction between wild‐type BLM and hRPA was necessary for unwinding reinitiation on hRPA‐coated DNA. The reported activities may facilitate BLM processing of stalled replication forks and illegitimately formed recombination intermediates. |
| doi_str_mv | 10.1038/emboj.2008.298 |
| format | Article |
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BLM
, encodes a member of the RecQ family of 3′–5′ DNA helicases, and is proposed to function in recombinational repair during DNA replication. Here, we have utilized single‐molecule fluorescence resonance energy transfer microscopy to examine the behaviour of BLM on forked DNA substrates. Strikingly, BLM unwound individual DNA molecules in a repetitive manner, unwinding a short length of duplex DNA followed by rapid reannealing and reinitiation of unwinding in several successions. Our results show that a monomeric BLM can ‘measure’ how many base pairs it has unwound, and once it has unwound a critical length, it reverses the unwinding reaction through strand switching and translocating on the opposing strand. Repetitive unwinding persisted even in the presence of hRPA, and interaction between wild‐type BLM and hRPA was necessary for unwinding reinitiation on hRPA‐coated DNA. The reported activities may facilitate BLM processing of stalled replication forks and illegitimately formed recombination intermediates.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2008.298</identifier><identifier>PMID: 19165145</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Bloom syndrome ; Bloom Syndrome - genetics ; Bloom Syndrome - metabolism ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - metabolism ; DNA Helicases - chemistry ; DNA Helicases - genetics ; DNA Repair ; DNA Replication ; Energy transfer ; Fluorescence ; Fluorescence Resonance Energy Transfer ; FRET ; Genetic disorders ; Genomics ; helicase ; hRPA ; Humans ; Microscopy ; Models, Genetic ; Molecular biology ; Nucleic Acid Conformation ; Oligonucleotides - chemistry ; Protein Binding ; RecQ Helicases - metabolism ; Resonance ; single molecule ; Substrates</subject><ispartof>The EMBO journal, 2009-02, Vol.28 (4), p.405-416</ispartof><rights>European Molecular Biology Organization 2009</rights><rights>Copyright © 2009 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Feb 18, 2009</rights><rights>Copyright © 2009, European Molecular Biology Organization 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6078-c30fc6806d7b9c8ad0d789797cae6fade18af9a724a85cc778a6de6be1a517033</citedby><cites>FETCH-LOGICAL-c6078-c30fc6806d7b9c8ad0d789797cae6fade18af9a724a85cc778a6de6be1a517033</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/PMC2646154/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646154/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2008.298$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19165145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yodh, Jaya G</creatorcontrib><creatorcontrib>Stevens, Benjamin C</creatorcontrib><creatorcontrib>Kanagaraj, Radhakrishnan</creatorcontrib><creatorcontrib>Janscak, Pavel</creatorcontrib><creatorcontrib>Ha, Taekjip</creatorcontrib><title>BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Bloom syndrome (BS) is a rare genetic disorder characterized by genomic instability and a high predisposition to cancer. The gene defective in BS,
BLM
, encodes a member of the RecQ family of 3′–5′ DNA helicases, and is proposed to function in recombinational repair during DNA replication. Here, we have utilized single‐molecule fluorescence resonance energy transfer microscopy to examine the behaviour of BLM on forked DNA substrates. Strikingly, BLM unwound individual DNA molecules in a repetitive manner, unwinding a short length of duplex DNA followed by rapid reannealing and reinitiation of unwinding in several successions. Our results show that a monomeric BLM can ‘measure’ how many base pairs it has unwound, and once it has unwound a critical length, it reverses the unwinding reaction through strand switching and translocating on the opposing strand. Repetitive unwinding persisted even in the presence of hRPA, and interaction between wild‐type BLM and hRPA was necessary for unwinding reinitiation on hRPA‐coated DNA. The reported activities may facilitate BLM processing of stalled replication forks and illegitimately formed recombination intermediates.</description><subject>Bloom syndrome</subject><subject>Bloom Syndrome - genetics</subject><subject>Bloom Syndrome - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA Helicases - chemistry</subject><subject>DNA Helicases - genetics</subject><subject>DNA Repair</subject><subject>DNA Replication</subject><subject>Energy transfer</subject><subject>Fluorescence</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>FRET</subject><subject>Genetic disorders</subject><subject>Genomics</subject><subject>helicase</subject><subject>hRPA</subject><subject>Humans</subject><subject>Microscopy</subject><subject>Models, Genetic</subject><subject>Molecular biology</subject><subject>Nucleic Acid Conformation</subject><subject>Oligonucleotides - chemistry</subject><subject>Protein Binding</subject><subject>RecQ Helicases - metabolism</subject><subject>Resonance</subject><subject>single molecule</subject><subject>Substrates</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUtvEzEUhS0EoqGwZYlGLLqb1J6HHxukNC0FlJao4rWzHM-dxGHGDvYMof8eDxOVgoTY2LLud8491kHoOcFTgnN-Cu3KbacZxnyaCf4ATUhBcZphVj5EE5xRkhaEiyP0JIQtxrjkjDxGR0QQWpKinCB9trhKNtAYrQIkLajQewjJ-fUs6e3e9bZKVlA7D0nYm05vjF0nofPKViGJR7K5Wc6SnXet66IsSoytBsaDsaYzqjPOPkWPatUEeHa4j9HH1xcf5m_SxfvLt_PZItUUM57qHNeackwrthKaqwpXjAsmmFZAa1UB4aoWimWF4qXWjHFFK6ArIKokDOf5MXo1-u76VQuVBhuDNnLnTav8rXTKyD8n1mzk2n2XGS0oKYtocHIw8O5bD6GTrQkamkZZcH2QlIpcMD5sevkXuHW9t_Fzkogy2uUii9B0hLR3IXio75IQLIfy5K_y5FCejOVFwYv7-X_jh7YiwEZgbxq4_Y-dvLg6ezc8RuvTURmiyK7B3wv8rzDpqDChgx93u5T_KinLWSk_X1_KL5_OlzfLBZXz_CfNysio</recordid><startdate>20090218</startdate><enddate>20090218</enddate><creator>Yodh, Jaya G</creator><creator>Stevens, Benjamin C</creator><creator>Kanagaraj, Radhakrishnan</creator><creator>Janscak, Pavel</creator><creator>Ha, Taekjip</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</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>AEUYN</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>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090218</creationdate><title>BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation</title><author>Yodh, Jaya G ; Stevens, Benjamin C ; Kanagaraj, Radhakrishnan ; Janscak, Pavel ; Ha, Taekjip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6078-c30fc6806d7b9c8ad0d789797cae6fade18af9a724a85cc778a6de6be1a517033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Bloom syndrome</topic><topic>Bloom Syndrome - genetics</topic><topic>Bloom Syndrome - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>DNA Helicases - chemistry</topic><topic>DNA Helicases - genetics</topic><topic>DNA Repair</topic><topic>DNA Replication</topic><topic>Energy transfer</topic><topic>Fluorescence</topic><topic>Fluorescence Resonance Energy Transfer</topic><topic>FRET</topic><topic>Genetic disorders</topic><topic>Genomics</topic><topic>helicase</topic><topic>hRPA</topic><topic>Humans</topic><topic>Microscopy</topic><topic>Models, Genetic</topic><topic>Molecular biology</topic><topic>Nucleic Acid Conformation</topic><topic>Oligonucleotides - chemistry</topic><topic>Protein Binding</topic><topic>RecQ Helicases - metabolism</topic><topic>Resonance</topic><topic>single molecule</topic><topic>Substrates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yodh, Jaya G</creatorcontrib><creatorcontrib>Stevens, Benjamin C</creatorcontrib><creatorcontrib>Kanagaraj, Radhakrishnan</creatorcontrib><creatorcontrib>Janscak, Pavel</creatorcontrib><creatorcontrib>Ha, Taekjip</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 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>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 Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</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>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Yodh, Jaya G</au><au>Stevens, Benjamin C</au><au>Kanagaraj, Radhakrishnan</au><au>Janscak, Pavel</au><au>Ha, Taekjip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2009-02-18</date><risdate>2009</risdate><volume>28</volume><issue>4</issue><spage>405</spage><epage>416</epage><pages>405-416</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Bloom syndrome (BS) is a rare genetic disorder characterized by genomic instability and a high predisposition to cancer. The gene defective in BS,
BLM
, encodes a member of the RecQ family of 3′–5′ DNA helicases, and is proposed to function in recombinational repair during DNA replication. Here, we have utilized single‐molecule fluorescence resonance energy transfer microscopy to examine the behaviour of BLM on forked DNA substrates. Strikingly, BLM unwound individual DNA molecules in a repetitive manner, unwinding a short length of duplex DNA followed by rapid reannealing and reinitiation of unwinding in several successions. Our results show that a monomeric BLM can ‘measure’ how many base pairs it has unwound, and once it has unwound a critical length, it reverses the unwinding reaction through strand switching and translocating on the opposing strand. Repetitive unwinding persisted even in the presence of hRPA, and interaction between wild‐type BLM and hRPA was necessary for unwinding reinitiation on hRPA‐coated DNA. The reported activities may facilitate BLM processing of stalled replication forks and illegitimately formed recombination intermediates.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>19165145</pmid><doi>10.1038/emboj.2008.298</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Bloom syndrome Bloom Syndrome - genetics Bloom Syndrome - metabolism Deoxyribonucleic acid DNA DNA - chemistry DNA - metabolism DNA Helicases - chemistry DNA Helicases - genetics DNA Repair DNA Replication Energy transfer Fluorescence Fluorescence Resonance Energy Transfer FRET Genetic disorders Genomics helicase hRPA Humans Microscopy Models, Genetic Molecular biology Nucleic Acid Conformation Oligonucleotides - chemistry Protein Binding RecQ Helicases - metabolism Resonance single molecule Substrates |
| title | BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation |
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