{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:29:59Z","timestamp":1791192599603,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T00:00:00Z","timestamp":1347494400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"DOI":"10.1038\/cddis.2012.120","type":"journal-article","created":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T06:04:13Z","timestamp":1347516253000},"page":"e390-e390","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["AIF-mediated caspase-independent necroptosis requires ATM and DNA-PK-induced histone H2AX Ser139 phosphorylation"],"prefix":"10.1038","volume":"3","author":[{"given":"M","family":"Baritaud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Cabon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Delavall\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Gal\u00e1n-Malo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-E","family":"Gilles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-N","family":"Brunelle-Navas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S A","family":"Susin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,9,13]]},"reference":[{"key":"BFcddis2012120_CR1","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/nrm2970","volume":"11","author":"P Vandenabeele","year":"2010","unstructured":"Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G . Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 2010; 11: 700\u2013714.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis2012120_CR2","doi-asserted-by":"publisher","first-page":"2592","DOI":"10.1101\/gad.1984410","volume":"24","author":"J Yuan","year":"2010","unstructured":"Yuan J, Kroemer G . Alternative cell death mechanisms in development and beyond. Genes Dev 2010; 24: 2592\u20132602.","journal-title":"Genes Dev"},{"key":"BFcddis2012120_CR3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/cdd.2011.164","volume":"19","author":"N Vanlangenakker","year":"2012","unstructured":"Vanlangenakker N, Vanden Berghe T, Vandenabeele P . Many stimuli pull the necrotic trigger, an overview. Cell Death Differ 2012; 19: 75\u201386.","journal-title":"Cell Death Differ"},{"key":"BFcddis2012120_CR4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nchembio.83","volume":"4","author":"A Degterev","year":"2008","unstructured":"Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4: 313\u2013321.","journal-title":"Nat Chem Biol"},{"key":"BFcddis2012120_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.cell.2011.11.031","volume":"148","author":"L Sun","year":"2012","unstructured":"Sun L, Wang H, Wang Z, He S, Chen S, Liao D et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 2012; 148: 213\u2013227.","journal-title":"Cell"},{"key":"BFcddis2012120_CR6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.cell.2011.11.030","volume":"148","author":"Z Wang","year":"2012","unstructured":"Wang Z, Jiang H, Chen S, Du F, Wang X . The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 2012; 148: 228\u2013243.","journal-title":"Cell"},{"key":"BFcddis2012120_CR7","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/iub.432","volume":"63","author":"L Delavallee","year":"2011","unstructured":"Delavallee L, Cabon L, Galan-Malo P, Lorenzo HK, Susin SA . AIF-mediated caspase-independent necroptosis: a new chance for targeted therapeutics. IUBMB Life 2011; 63: 221\u2013232.","journal-title":"IUBMB Life"},{"key":"BFcddis2012120_CR8","doi-asserted-by":"publisher","first-page":"8788","DOI":"10.1074\/jbc.M508135200","volume":"281","author":"Y Xu","year":"2006","unstructured":"Xu Y, Huang S, Liu ZG, Han J . Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1\/TRAF2-mediated JNK1 activation. J Biol Chem 2006; 281: 8788\u20138795.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR9","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/cdd.2011.91","volume":"19","author":"L Cabon","year":"2012","unstructured":"Cabon L, Galan-Malo P, Bouharrour A, Delavallee L, Brunelle-Navas MN, Lorenzo HK et al. BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation. Cell Death Differ 2012; 19: 245\u2013256.","journal-title":"Cell Death Differ"},{"key":"BFcddis2012120_CR10","doi-asserted-by":"publisher","first-page":"4844","DOI":"10.1128\/MCB.02141-06","volume":"27","author":"RS Moubarak","year":"2007","unstructured":"Moubarak RS, Yuste VJ, Artus C, Bouharrour A, Greer PA, Menissier-de Murcia J et al. Sequential activation of poly(ADP-Ribose) polymerase 1, Calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol Cell Biol 2007; 27: 4844\u20134862.","journal-title":"Mol Cell Biol"},{"key":"BFcddis2012120_CR11","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1038\/emboj.2010.43","volume":"29","author":"C Artus","year":"2010","unstructured":"Artus C, Boujrad H, Bouharrour A, Brunelle MN, Hoos S, Yuste VJ et al. AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX. EMBO J 2010; 29: 1585\u20131599.","journal-title":"EMBO J"},{"key":"BFcddis2012120_CR12","doi-asserted-by":"publisher","first-page":"3166","DOI":"10.4161\/cc.9.16.12552","volume":"9","author":"M Baritaud","year":"2010","unstructured":"Baritaud M, Boujrad H, Lorenzo HK, Krantic S, Susin SA . Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis. Cell Cycle 2010; 9: 3166\u20133173.","journal-title":"Cell Cycle"},{"key":"BFcddis2012120_CR13","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1038\/sj.cdd.4401687","volume":"12","author":"VJ Yuste","year":"2005","unstructured":"Yuste VJ, Moubarak RS, Delettre C, Bras M, Sancho P, Robert N et al. Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release. Cell Death Differ 2005; 12: 1445\u20131448.","journal-title":"Cell Death Differ"},{"key":"BFcddis2012120_CR14","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.dnarep.2004.03.024","volume":"3","author":"O Fernandez-Capetillo","year":"2004","unstructured":"Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A . H2AX: the histone guardian of the genome. DNA Repair (Amst) 2004; 3: 959\u2013967.","journal-title":"DNA Repair (Amst)"},{"key":"BFcddis2012120_CR15","doi-asserted-by":"publisher","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","volume":"273","author":"EP Rogakou","year":"1998","unstructured":"Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM . DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998; 273: 5858\u20135868.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR16","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/nrc2523","volume":"8","author":"WM Bonner","year":"2008","unstructured":"Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, Solier S et al. GammaH2AX and cancer. Nat Rev Cancer 2008; 8: 957\u2013967.","journal-title":"Nat Rev Cancer"},{"key":"BFcddis2012120_CR17","doi-asserted-by":"publisher","first-page":"426","DOI":"10.4161\/cc.2.5.509","volume":"2","author":"O Fernandez-Capetillo","year":"2003","unstructured":"Fernandez-Capetillo O, Celeste A, Nussenzweig A . Focusing on foci: H2AX and the recruitment of DNA-damage response factors. Cell Cycle 2003; 2: 426\u2013427.","journal-title":"Cell Cycle"},{"key":"BFcddis2012120_CR18","doi-asserted-by":"publisher","first-page":"9390","DOI":"10.1074\/jbc.275.13.9390","volume":"275","author":"EP Rogakou","year":"2000","unstructured":"Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM . Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 2000; 275: 9390\u20139395.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.molcel.2006.05.023","volume":"23","author":"C Lu","year":"2006","unstructured":"Lu C, Zhu F, Cho YY, Tang F, Zykova T, Ma WY et al. Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol Cell 2006; 23: 121\u201332.","journal-title":"Mol Cell"},{"key":"BFcddis2012120_CR20","doi-asserted-by":"publisher","first-page":"39108","DOI":"10.1074\/jbc.M110.151753","volume":"285","author":"W Wen","year":"2011","unstructured":"Wen W, Zhu F, Zhang J, Keum YS, Zykova T, Yao K et al. MST1 promotes apoptosis through phosphorylation of histone H2AX. J Biol Chem 2011; 285: 39108\u201339116.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR21","doi-asserted-by":"publisher","first-page":"42462","DOI":"10.1074\/jbc.C100466200","volume":"276","author":"S Burma","year":"2001","unstructured":"Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ . ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001; 276: 42462\u201342467.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR22","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.dnarep.2006.01.011","volume":"5","author":"B Mukherjee","year":"2006","unstructured":"Mukherjee B, Kessinger C, Kobayashi J, Chen BP, Chen DJ, Chatterjee A et al. DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. DNA Repair (Amst) 2006; 5: 575\u2013590.","journal-title":"DNA Repair (Amst)"},{"key":"BFcddis2012120_CR23","doi-asserted-by":"publisher","first-page":"47759","DOI":"10.1074\/jbc.C100569200","volume":"276","author":"IM Ward","year":"2001","unstructured":"Ward IM, Chen J . Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 2001; 276: 47759\u201347762.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR24","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.4161\/cc.6.21.4842","volume":"6","author":"H Boujrad","year":"2007","unstructured":"Boujrad H, Gubkina O, Robert N, Krantic S, Susin SA . AIF-mediated programmed necrosis: a highly regulated way to die. Cell Cycle 2007; 6: 2612\u20132619.","journal-title":"Cell Cycle"},{"key":"BFcddis2012120_CR25","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1083\/jcb.146.5.905","volume":"146","author":"EP Rogakou","year":"1999","unstructured":"Rogakou EP, Boon C, Redon C, Bonner WM . Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 1999; 146: 905\u2013916.","journal-title":"J Cell Biol"},{"key":"BFcddis2012120_CR26","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.molcel.2005.05.008","volume":"18","author":"C Thiriet","year":"2005","unstructured":"Thiriet C, Hayes JJ . Chromatin in need of a fix: phosphorylation of H2AX connects chromatin to DNA repair. Mol Cell 2005; 18: 617\u2013622.","journal-title":"Mol Cell"},{"key":"BFcddis2012120_CR27","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0092-8674(03)00567-1","volume":"114","author":"A Celeste","year":"2003","unstructured":"Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA et al. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 2003; 114: 371\u2013383.","journal-title":"Cell"},{"key":"BFcddis2012120_CR28","doi-asserted-by":"publisher","first-page":"9152","DOI":"10.1158\/0008-5472.CAN-04-2727","volume":"64","author":"I Hickson","year":"2004","unstructured":"Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr AI et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 2004; 64: 9152\u20139159.","journal-title":"Cancer Res"},{"key":"BFcddis2012120_CR29","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nsmb.2076","volume":"18","author":"LI Toledo","year":"2011","unstructured":"Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S et al. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol 2011; 18: 721\u2013727.","journal-title":"Nat Struct Mol Biol"},{"key":"BFcddis2012120_CR30","first-page":"6008","volume":"63","author":"SJ Veuger","year":"2003","unstructured":"Veuger SJ, Curtin NJ, Richardson CJ, Smith GC, Durkacz BW . Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res 2003; 63: 6008\u20136015.","journal-title":"Cancer Res"},{"key":"BFcddis2012120_CR31","doi-asserted-by":"publisher","first-page":"13681","DOI":"10.1073\/pnas.251194298","volume":"98","author":"BL Bennett","year":"2001","unstructured":"Bennett BL, Sasaki DT, Murray BW, O\u2019Leary EC, Sakata ST, Xu W et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA 2001; 98: 13681\u201313686.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2012120_CR32","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1016\/j.dnarep.2008.07.006","volume":"7","author":"PS Kedar","year":"2008","unstructured":"Kedar PS, Stefanick DF, Horton JK, Wilson SH . Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by PARP inhibition. DNA Repair (Amst) 2008; 7: 1787\u20131798.","journal-title":"DNA Repair (Amst)"},{"key":"BFcddis2012120_CR33","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature01368","volume":"421","author":"CJ Bakkenist","year":"2003","unstructured":"Bakkenist CJ, Kastan MB . DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003; 421: 499\u2013506.","journal-title":"Nature"},{"key":"BFcddis2012120_CR34","doi-asserted-by":"publisher","first-page":"14709","DOI":"10.1074\/jbc.M408827200","volume":"280","author":"BP Chen","year":"2005","unstructured":"Chen BP, Chan DW, Kobayashi J, Burma S, Asaithamby A, Morotomi-Yano K et al. Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J Biol Chem 2005; 280: 14709\u201314715.","journal-title":"J Biol Chem"},{"key":"BFcddis2012120_CR35","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/47412","volume":"403","author":"BD Strahl","year":"2000","unstructured":"Strahl BD, Allis CD . The language of covalent histone modifications. Nature 2000; 403: 41\u201345.","journal-title":"Nature"},{"key":"BFcddis2012120_CR36","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1128\/MCB.00581-08","volume":"29","author":"S Solier","year":"2009","unstructured":"Solier S, Sordet O, Kohn KW, Pommier Y . Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways. Mol Cell Biol 2009; 29: 68\u201382.","journal-title":"Mol Cell Biol"},{"key":"BFcddis2012120_CR37","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1038\/35050000","volume":"408","author":"JA Downs","year":"2000","unstructured":"Downs JA, Lowndes NF, Jackson SP . A role for saccharomyces cerevisiae histone H2A in DNA repair. Nature 2000; 408: 1001\u20131004.","journal-title":"Nature"},{"key":"BFcddis2012120_CR38","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1083\/jcb.200510015","volume":"172","author":"MJ Kruhlak","year":"2006","unstructured":"Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, Muller WG, McNally JG et al. Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J Cell Biol 2006; 172: 823\u2013834.","journal-title":"J Cell Biol"},{"key":"BFcddis2012120_CR39","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.dnarep.2009.04.006","volume":"8","author":"CA Lovejoy","year":"2009","unstructured":"Lovejoy CA, Cortez D . Common mechanisms of PIKK regulation. DNA Repair (Amst) 2009; 8: 1004\u20131008.","journal-title":"DNA Repair (Amst)"},{"key":"BFcddis2012120_CR40","doi-asserted-by":"publisher","first-page":"16441","DOI":"10.1074\/jbc.M608406200","volume":"282","author":"JF Haince","year":"2007","unstructured":"Haince JF, Kozlov S, Dawson VL, Dawson TM, Hendzel MJ, Lavin MF et al. Ataxia telangiectasia mutated (ATM) signaling network is modulated by a novel poly(ADP-ribose)-dependent pathway in the early response to DNA-damaging agents. J Biol Chem 2007; 282: 16441\u201316453.","journal-title":"J Biol Chem"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cddis2012120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cddis2012120","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2012120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T18:38:49Z","timestamp":1672943929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2012120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,13]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2012,9]]}},"alternative-id":["BFcddis2012120"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2012.120","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,13]]},"assertion":[{"value":"22 May 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2012","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}