Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 Complexes
Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities w...
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| Veröffentlicht in: | Molecular cell 2007-03, Vol.25 (5), p.647-661 |
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| container_title | Molecular cell |
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| creator | Bhaskara, Venugopal Dupré, Aude Lengsfeld, Bettina Hopkins, Ben B. Chan, Angela Lee, Ji-Hoon Zhang, Xiaoming Gautier, Jean Zakian, Virginia Paull, Tanya T. |
| description | Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a
rad50 null strain with respect to meiosis and telomere maintenance in
S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions. |
| doi_str_mv | 10.1016/j.molcel.2007.01.028 |
| format | Article |
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rad50 null strain with respect to meiosis and telomere maintenance in
S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2007.01.028</identifier><identifier>PMID: 17349953</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acid Anhydride Hydrolases ; Adenine - metabolism ; Adenosine Triphosphate - metabolism ; Adenylate Kinase - antagonists & inhibitors ; Adenylate Kinase - metabolism ; Amino Acid Motifs ; Animals ; Archaeal Proteins - metabolism ; Catalysis - drug effects ; Dinucleoside Phosphates - metabolism ; DNA ; DNA - metabolism ; DNA Repair Enzymes - metabolism ; DNA-Binding Proteins - metabolism ; Endodeoxyribonucleases - metabolism ; Enzyme Inhibitors - pharmacology ; Exodeoxyribonucleases - metabolism ; Humans ; Hydrolysis - drug effects ; MRE11 Homologue Protein ; Mutant Proteins - metabolism ; Mutation - genetics ; Pyrococcus furiosus - drug effects ; Pyrococcus furiosus - enzymology ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae Proteins - metabolism ; Xenopus</subject><ispartof>Molecular cell, 2007-03, Vol.25 (5), p.647-661</ispartof><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-1f36cee46a26e5362348693e62fe825459cd951d73b69f17a1ccd01502d862d13</citedby><cites>FETCH-LOGICAL-c461t-1f36cee46a26e5362348693e62fe825459cd951d73b69f17a1ccd01502d862d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276507000512$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17349953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhaskara, Venugopal</creatorcontrib><creatorcontrib>Dupré, Aude</creatorcontrib><creatorcontrib>Lengsfeld, Bettina</creatorcontrib><creatorcontrib>Hopkins, Ben B.</creatorcontrib><creatorcontrib>Chan, Angela</creatorcontrib><creatorcontrib>Lee, Ji-Hoon</creatorcontrib><creatorcontrib>Zhang, Xiaoming</creatorcontrib><creatorcontrib>Gautier, Jean</creatorcontrib><creatorcontrib>Zakian, Virginia</creatorcontrib><creatorcontrib>Paull, Tanya T.</creatorcontrib><title>Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 Complexes</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a
rad50 null strain with respect to meiosis and telomere maintenance in
S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions.</description><subject>Acid Anhydride Hydrolases</subject><subject>Adenine - metabolism</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Adenylate Kinase - antagonists & inhibitors</subject><subject>Adenylate Kinase - metabolism</subject><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Archaeal Proteins - metabolism</subject><subject>Catalysis - drug effects</subject><subject>Dinucleoside Phosphates - metabolism</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endodeoxyribonucleases - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Exodeoxyribonucleases - metabolism</subject><subject>Humans</subject><subject>Hydrolysis - drug effects</subject><subject>MRE11 Homologue Protein</subject><subject>Mutant Proteins - metabolism</subject><subject>Mutation - genetics</subject><subject>Pyrococcus furiosus - drug effects</subject><subject>Pyrococcus furiosus - enzymology</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - enzymology</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Xenopus</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1vEzEQtRCIlsI_QGhP3LKd8deuL0hRoIAoLarK2XLs2dTRfgR7EzX_no0SUbhwmpHezHsz7zH2FqFEQH25Lruh9dSWHKAqAUvg9TN2jmCqmUQtn596Xml1xl7lvAZAqWrzkp1hJaQxSpyzH3cuKCjmgfp960YqvsXeZSrmfoy7OO6LO1ptD0AuPt7Mi3saHyjFflUs98X3RIiXR4LF0G1aeqT8mr1oXJvpzalesJ9Xn-4XX2bXt5-_LubXMy81jjNshPZEUjuuSQnNhay1EaR5QzVXUhkfjMJQiaU2DVYOvQ-ACnioNQ8oLtiHI-9mu-woeOrH5Fq7SbFzaW8HF-2_SB8f7GrYWQEKQPKJ4P2JIA2_tpRH28U8-dm6noZtthVwxU0tpkF5HPRpyDlR80cEwR6isGt7jMIeorCAdopiWnv394FPSyfvnz6gyaZdpGSzj9R7CjGRH20Y4v8VfgNS0Zst</recordid><startdate>20070309</startdate><enddate>20070309</enddate><creator>Bhaskara, Venugopal</creator><creator>Dupré, Aude</creator><creator>Lengsfeld, Bettina</creator><creator>Hopkins, Ben B.</creator><creator>Chan, Angela</creator><creator>Lee, Ji-Hoon</creator><creator>Zhang, Xiaoming</creator><creator>Gautier, Jean</creator><creator>Zakian, Virginia</creator><creator>Paull, Tanya T.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070309</creationdate><title>Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 Complexes</title><author>Bhaskara, Venugopal ; 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The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a
rad50 null strain with respect to meiosis and telomere maintenance in
S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17349953</pmid><doi>10.1016/j.molcel.2007.01.028</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Acid Anhydride Hydrolases Adenine - metabolism Adenosine Triphosphate - metabolism Adenylate Kinase - antagonists & inhibitors Adenylate Kinase - metabolism Amino Acid Motifs Animals Archaeal Proteins - metabolism Catalysis - drug effects Dinucleoside Phosphates - metabolism DNA DNA - metabolism DNA Repair Enzymes - metabolism DNA-Binding Proteins - metabolism Endodeoxyribonucleases - metabolism Enzyme Inhibitors - pharmacology Exodeoxyribonucleases - metabolism Humans Hydrolysis - drug effects MRE11 Homologue Protein Mutant Proteins - metabolism Mutation - genetics Pyrococcus furiosus - drug effects Pyrococcus furiosus - enzymology Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae Proteins - metabolism Xenopus |
| title | Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 Complexes |
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