HARP Is an ATP-Driven Annealing Helicase
DNA-dependent adenosine triphosphatases (ATPases) participate in a broad range of biological processes including transcription, DNA repair, and chromatin dynamics. Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2008-10, Vol.322 (5902), p.748-750 |
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description | DNA-dependent adenosine triphosphatases (ATPases) participate in a broad range of biological processes including transcription, DNA repair, and chromatin dynamics. Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus. |
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Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1161233</identifier><identifier>PMID: 18974355</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adenosine triphosphatase ; Adenosine triphosphatases ; Adenosine Triphosphatases - chemistry ; Adenosine Triphosphatases - metabolism ; Adenosine Triphosphate - metabolism ; Annealing ; Deoxyribonucleic acid ; DNA ; DNA Helicases - chemistry ; DNA Helicases - deficiency ; DNA Helicases - genetics ; DNA Helicases - metabolism ; DNA, Single-Stranded - chemistry ; DNA, Single-Stranded - metabolism ; DNA-Binding Proteins ; Gels ; Genetic mutation ; Harps ; Humans ; Immunologic Deficiency Syndromes - genetics ; Molecular biology ; Mutant Proteins - metabolism ; Mutation ; Nuclear Proteins - metabolism ; Nucleic Acid Conformation ; Osteochondrodysplasias - genetics ; Plasmids ; Proteins ; Replication Protein A - metabolism ; Syndrome</subject><ispartof>Science (American Association for the Advancement of Science), 2008-10, Vol.322 (5902), p.748-750</ispartof><rights>Copyright 2008 American Association for the Advancement of Science</rights><rights>Copyright © 2008, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-da94f565e7e4c06103386899d65ea6bf20e8336698f972ea71e08808987d040b3</citedby><cites>FETCH-LOGICAL-c623t-da94f565e7e4c06103386899d65ea6bf20e8336698f972ea71e08808987d040b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20145178$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20145178$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18974355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yusufzai, Timur</creatorcontrib><creatorcontrib>Kadonaga, James T</creatorcontrib><title>HARP Is an ATP-Driven Annealing Helicase</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>DNA-dependent adenosine triphosphatases (ATPases) participate in a broad range of biological processes including transcription, DNA repair, and chromatin dynamics. Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.</description><subject>Adenosine triphosphatase</subject><subject>Adenosine triphosphatases</subject><subject>Adenosine Triphosphatases - chemistry</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Annealing</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Helicases - chemistry</subject><subject>DNA Helicases - deficiency</subject><subject>DNA Helicases - genetics</subject><subject>DNA Helicases - metabolism</subject><subject>DNA, Single-Stranded - chemistry</subject><subject>DNA, Single-Stranded - metabolism</subject><subject>DNA-Binding Proteins</subject><subject>Gels</subject><subject>Genetic mutation</subject><subject>Harps</subject><subject>Humans</subject><subject>Immunologic Deficiency Syndromes - genetics</subject><subject>Molecular biology</subject><subject>Mutant Proteins - metabolism</subject><subject>Mutation</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nucleic Acid Conformation</subject><subject>Osteochondrodysplasias - genetics</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Replication Protein A - metabolism</subject><subject>Syndrome</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoiHlzAmIOEAv2449668LUlQKqVSpFbRny9nMBkcbb7GTSv33dZVVCxzakz-ex2OPX8becTjkXKij3ASKDZWF4gLxBRtxsLKyAvAlGwGgqgxoucfe5LwCKMzia7bHjdU1SjliB7Ppz4vJaZ74OJleXlTfUrihMo2RfBficjKjLjQ-0z571fou09thHLOr7yeXx7Pq7PzH6fH0rGqUwE218LZupZKkqW5AcUA0yli7KFtezVsBZBCVsqa1WpDXnMAYMNboBdQwxzH7uqt7vZ2vadFQ3CTfuesU1j7dut4H9y-J4bdb9jdOSKNluW7MvgwFUv9nS3nj1iE31HU-Ur_NrjQuUBuhi_n5SVNZjRZAPStyq7lFhCJ--k9c9dsUy385wVHeO7xIRzupSX3OidqH5ji4-1TdkKobUi0nPvz9J4_-EGMR3u-EVd706YEL4LXk2hT-ccdb3zu_TCG7q1-FludIKWtV4x2C0K2s</recordid><startdate>20081031</startdate><enddate>20081031</enddate><creator>Yusufzai, Timur</creator><creator>Kadonaga, James T</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081031</creationdate><title>HARP Is an ATP-Driven Annealing Helicase</title><author>Yusufzai, Timur ; 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Mutations in the HepA-related protein (HARP) ATPase are responsible for Schimke immuno-osseous dysplasia (SIOD), but the function of the protein is unknown. We found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A. Other related ATPases, including the DNA translocase Rad54, did not exhibit annealing helicase activity. Analysis of mutant HARP proteins suggests that SIOD is caused by a deficiency in annealing helicase activity. Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>18974355</pmid><doi>10.1126/science.1161233</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenosine triphosphatase Adenosine triphosphatases Adenosine Triphosphatases - chemistry Adenosine Triphosphatases - metabolism Adenosine Triphosphate - metabolism Annealing Deoxyribonucleic acid DNA DNA Helicases - chemistry DNA Helicases - deficiency DNA Helicases - genetics DNA Helicases - metabolism DNA, Single-Stranded - chemistry DNA, Single-Stranded - metabolism DNA-Binding Proteins Gels Genetic mutation Harps Humans Immunologic Deficiency Syndromes - genetics Molecular biology Mutant Proteins - metabolism Mutation Nuclear Proteins - metabolism Nucleic Acid Conformation Osteochondrodysplasias - genetics Plasmids Proteins Replication Protein A - metabolism Syndrome |
title | HARP Is an ATP-Driven Annealing Helicase |
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