DNase γ is the effector endonuclease for internucleosomal DNA fragmentation in necrosis
Apoptosis and necrosis, two major forms of cell death, can be distinguished morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the maj...
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| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e80223 |
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| creator | Mizuta, Ryushin Araki, Shinsuke Furukawa, Makoto Furukawa, Yuki Ebara, Syota Shiokawa, Daisuke Hayashi, Katsuhiko Tanuma, Sei-ichi Kitamura, Daisuke |
| description | Apoptosis and necrosis, two major forms of cell death, can be distinguished morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to generate INDF but its role among other apoptosis-associated endonucleases in cell death is unclear. Here we show that (i) INDF occurs even during necrosis in cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase γ, but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis. These results document a previously unappreciated role for INDF in necrosis and define its molecular basis. |
| doi_str_mv | 10.1371/journal.pone.0080223 |
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Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to generate INDF but its role among other apoptosis-associated endonucleases in cell death is unclear. Here we show that (i) INDF occurs even during necrosis in cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase γ, but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis. These results document a previously unappreciated role for INDF in necrosis and define its molecular basis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0080223</identifier><identifier>PMID: 24312463</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal tissues ; Animals ; Apoptosis ; Biochemistry ; Calcium ; Cancer ; Caspase ; Cell death ; Cell lines ; Cytotoxicity ; Deoxyribonuclease ; Deoxyribonucleases - genetics ; Deoxyribonucleases - metabolism ; Deoxyribonucleic acid ; DNA ; DNA Fragmentation ; Endodeoxyribonucleases - genetics ; Endodeoxyribonucleases - metabolism ; Endonuclease ; Endoplasmic reticulum ; Fragmentation ; Gangrene ; Humans ; Magnesium ; Mice ; Necrosis ; Pharmaceutical sciences ; Physiology ; Poly-ADP-Ribose Binding Proteins ; Rodents ; U937 Cells</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e80223</ispartof><rights>2013 Mizuta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Mizuta et al 2013 Mizuta et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-50627f53fbaa2b45f6969a1273fbea938369b836b417ad0b3962f2b2d274d9b73</citedby><cites>FETCH-LOGICAL-c526t-50627f53fbaa2b45f6969a1273fbea938369b836b417ad0b3962f2b2d274d9b73</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/PMC3846476/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846476/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24312463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mizuta, Ryushin</creatorcontrib><creatorcontrib>Araki, Shinsuke</creatorcontrib><creatorcontrib>Furukawa, Makoto</creatorcontrib><creatorcontrib>Furukawa, Yuki</creatorcontrib><creatorcontrib>Ebara, Syota</creatorcontrib><creatorcontrib>Shiokawa, Daisuke</creatorcontrib><creatorcontrib>Hayashi, Katsuhiko</creatorcontrib><creatorcontrib>Tanuma, Sei-ichi</creatorcontrib><creatorcontrib>Kitamura, Daisuke</creatorcontrib><title>DNase γ is the effector endonuclease for internucleosomal DNA fragmentation in necrosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Apoptosis and necrosis, two major forms of cell death, can be distinguished morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to generate INDF but its role among other apoptosis-associated endonucleases in cell death is unclear. Here we show that (i) INDF occurs even during necrosis in cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase γ, but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis. These results document a previously unappreciated role for INDF in necrosis and define its molecular basis.</description><subject>Animal tissues</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Caspase</subject><subject>Cell death</subject><subject>Cell lines</subject><subject>Cytotoxicity</subject><subject>Deoxyribonuclease</subject><subject>Deoxyribonucleases - genetics</subject><subject>Deoxyribonucleases - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Fragmentation</subject><subject>Endodeoxyribonucleases - genetics</subject><subject>Endodeoxyribonucleases - metabolism</subject><subject>Endonuclease</subject><subject>Endoplasmic reticulum</subject><subject>Fragmentation</subject><subject>Gangrene</subject><subject>Humans</subject><subject>Magnesium</subject><subject>Mice</subject><subject>Necrosis</subject><subject>Pharmaceutical sciences</subject><subject>Physiology</subject><subject>Poly-ADP-Ribose Binding Proteins</subject><subject>Rodents</subject><subject>U937 Cells</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUtRCIlsIfIIjEhs0MfsWON0hVy6NSVTYgsbNuHHvqUWIPdoLEd_Ef_aY6M2nVIja2de65595jHYReE7wmTJIP2zilAP16F4NdY9xgStkTdEwUoytBMXv64H2EXuS8xbhmjRDP0RHljFAu2DH6eX4F2VY3fyufq_HaVtY5a8aYKhu6GCbT27nuCuDDaNMeiTkO0FfnV6eVS7AZbBhh9DEUShWsSTH7_BI9c9Bn-2q5T9CPz5--n31dXX77cnF2erkyNRXjqsaCSlcz1wLQltdOKKGAUFkQC4o1TKi2HC0nEjrcMiWooy3tqOSdaiU7QW8Purs-Zr18StakuMNKKowL4-LA6CJs9S75AdIfHcHrPRDTRkMaffGlgTJJZeeEM4YTU5bCgMtkaQ02xoii9XGZNrWD7UxxnqB_JPq4Evy13sTfmjVccDkLvF8EUvw12TzqwWdj-x6CjdN-77oRNWW0UN_9Q_2_O35gzd-ek3X3yxCs56Dcdek5KHoJSml789DIfdNdMtgtdNu9QA</recordid><startdate>20131202</startdate><enddate>20131202</enddate><creator>Mizuta, Ryushin</creator><creator>Araki, Shinsuke</creator><creator>Furukawa, Makoto</creator><creator>Furukawa, Yuki</creator><creator>Ebara, Syota</creator><creator>Shiokawa, Daisuke</creator><creator>Hayashi, Katsuhiko</creator><creator>Tanuma, Sei-ichi</creator><creator>Kitamura, Daisuke</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131202</creationdate><title>DNase γ is the effector endonuclease for internucleosomal DNA fragmentation in necrosis</title><author>Mizuta, Ryushin ; Araki, Shinsuke ; Furukawa, Makoto ; Furukawa, Yuki ; Ebara, Syota ; Shiokawa, Daisuke ; Hayashi, Katsuhiko ; Tanuma, Sei-ichi ; Kitamura, Daisuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-50627f53fbaa2b45f6969a1273fbea938369b836b417ad0b3962f2b2d274d9b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal tissues</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Caspase</topic><topic>Cell death</topic><topic>Cell lines</topic><topic>Cytotoxicity</topic><topic>Deoxyribonuclease</topic><topic>Deoxyribonucleases - 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Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to generate INDF but its role among other apoptosis-associated endonucleases in cell death is unclear. Here we show that (i) INDF occurs even during necrosis in cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase γ, but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis. These results document a previously unappreciated role for INDF in necrosis and define its molecular basis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24312463</pmid><doi>10.1371/journal.pone.0080223</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animal tissues Animals Apoptosis Biochemistry Calcium Cancer Caspase Cell death Cell lines Cytotoxicity Deoxyribonuclease Deoxyribonucleases - genetics Deoxyribonucleases - metabolism Deoxyribonucleic acid DNA DNA Fragmentation Endodeoxyribonucleases - genetics Endodeoxyribonucleases - metabolism Endonuclease Endoplasmic reticulum Fragmentation Gangrene Humans Magnesium Mice Necrosis Pharmaceutical sciences Physiology Poly-ADP-Ribose Binding Proteins Rodents U937 Cells |
| title | DNase γ is the effector endonuclease for internucleosomal DNA fragmentation in necrosis |
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