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Mitochondrial tyrosyl-DNA phosphodiesterase 2 and its TDP2S short isoform.

Huang SN, Dalla Rosa I, Michaels SA, Tulumello DV, Agama K, Khiati S, Jean SR, Baechler SA, Factor VM, Varma S, Murai J, Miller Jenkins LM, Kelley SO, Pommier Y.

EMBO Rep. 2018 Feb 9. pii: e42139. doi: 10.15252/embr.201642139. [Epub ahead of print]


SLFN11 Blocks Stressed Replication Forks Independently of ATR.

Murai J, Tang SW, Leo E, Baechler SA, Redon CE, Zhang H, Al Abo M, Rajapakse VN, Nakamura E, Jenkins LMM, Aladjem MI, Pommier Y.

Mol Cell. 2018 Feb 1;69(3):371-384.e6. doi: 10.1016/j.molcel.2018.01.012.


Overcoming resistance to DNA targeted agents by epigenetic activation of Schlafen 11 (SLFN11) expression with class I histone deacetylase inhibitors.

Tang SW, Thomas A, Murai J, Trepel J, Bates SE, Rajapakse VN, Pommier Y.

Clin Cancer Res. 2018 Feb 1. pii: clincanres.0443.2017. doi: 10.1158/1078-0432.CCR-17-0443. [Epub ahead of print]


Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors.

Thomas A, Redon CE, Sciuto L, Padiernos E, Ji J, Lee MJ, Yuno A, Lee S, Zhang Y, Tran L, Yutzy W, Rajan A, Guha U, Chen H, Hassan R, Alewine CC, Szabo E, Bates SE, Kinders RJ, Steinberg SM, Doroshow JH, Aladjem MI, Trepel JB, Pommier Y.

J Clin Oncol. 2017 Dec 18:JCO2017766915. doi: 10.1200/JCO.2017.76.6915. [Epub ahead of print]


ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair.

Tsuda M, Cho K, Ooka M, Shimizu N, Watanabe R, Yasui A, Nakazawa Y, Ogi T, Harada H, Agama K, Nakamura J, Asada R, Fujiike H, Sakuma T, Yamamoto T, Murai J, Hiraoka M, Koike K, Pommier Y, Takeda S, Hirota K.

PLoS One. 2017 Nov 17;12(11):e0188320. doi: 10.1371/journal.pone.0188320. eCollection 2017.


Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition activity of novel piperidinyl sulfamides.

Jun JH, Kumar V, Dexheimer TS, Wedlich I, Nicklaus MC, Pommier Y, Malhotra SV.

Eur J Pharm Sci. 2018 Jan 1;111:337-348. doi: 10.1016/j.ejps.2017.10.017. Epub 2017 Oct 13.


Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.

Dalla Rosa I, Zhang H, Khiati S, Wu X, Pommier Y.

J Biol Chem. 2017 Dec 8;292(49):20162-20172. doi: 10.1074/jbc.M117.815241. Epub 2017 Oct 11.


HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia.

Takiuchi Y, Kobayashi M, Tada K, Iwai F, Sakurada M, Hirabayashi S, Nagata K, Shirakawa K, Shindo K, Yasunaga JI, Murakawa Y, Rajapakse V, Pommier Y, Matsuoka M, Takaori-Kondo A.

Sci Rep. 2017 Oct 9;7(1):12849. doi: 10.1038/s41598-017-12924-0.


Report on the first SLFN11 monothematic workshop: from function to role as a biomarker in cancer.

Ballestrero A, Bedognetti D, Ferraioli D, Franceschelli P, Labidi-Galy SI, Leo E, Murai J, Pommier Y, Tsantoulis P, Vellone VG, Zoppoli G.

J Transl Med. 2017 Oct 2;15(1):199. doi: 10.1186/s12967-017-1296-3.


Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.

Sloan R, Huang SN, Pommier Y, Jinks-Robertson S.

DNA Repair (Amst). 2017 Nov;59:69-75. doi: 10.1016/j.dnarep.2017.09.004. Epub 2017 Sep 18.


Distribution bias and biochemical characterization of TOP1MT single nucleotide variants.

Zhang H, Seol Y, Agama K, Neuman KC, Pommier Y.

Sci Rep. 2017 Aug 17;7(1):8614. doi: 10.1038/s41598-017-09258-2.


TDP1 is Critical for the Repair of DNA Breaks Induced by Sapacitabine, a Nucleoside also Targeting ATM- and BRCA-Deficient Tumors.

Abo MA, Sasanuma H, Liu X, Rajapakse VN, Huang SY, Kiselev E, Takeda S, Plunkett W, Pommier Y.

Mol Cancer Ther. 2017 Nov;16(11):2543-2551. doi: 10.1158/1535-7163.MCT-17-0110. Epub 2017 Aug 11.


Structure-Guided Optimization of HIV Integrase Strand Transfer Inhibitors.

Zhao XZ, Smith SJ, Maskell DP, Métifiot M, Pye VE, Fesen K, Marchand C, Pommier Y, Cherepanov P, Hughes SH, Burke TR Jr.

J Med Chem. 2017 Sep 14;60(17):7315-7332. doi: 10.1021/acs.jmedchem.7b00596. Epub 2017 Aug 10.


Genome Organization Drives Chromosome Fragility.

Canela A, Maman Y, Jung S, Wong N, Callen E, Day A, Kieffer-Kwon KR, Pekowska A, Zhang H, Rao SSP, Huang SC, Mckinnon PJ, Aplan PD, Pommier Y, Aiden EL, Casellas R, Nussenzweig A.

Cell. 2017 Jul 27;170(3):507-521.e18. doi: 10.1016/j.cell.2017.06.034. Epub 2017 Jul 20.


Identification of Natural Products That Inhibit the Catalytic Function of Human Tyrosyl-DNA Phosphodiesterase (TDP1).

Bermingham A, Price E, Marchand C, Chergui A, Naumova A, Whitson EL, Krumpe LRH, Goncharova EI, Evans JR, McKee TC, Henrich CJ, Pommier Y, O'Keefe BR.

SLAS Discov. 2017 Jul 1:2472555217717200. doi: 10.1177/2472555217717200. [Epub ahead of print]


Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents That Inhibit Topoisomerase I.

Elsayed MSA, Su Y, Wang P, Sethi T, Agama K, Ravji A, Redon CE, Kiselev E, Horzmann KA, Freeman JL, Pommier Y, Cushman M.

J Med Chem. 2017 Jul 13;60(13):5364-5376. doi: 10.1021/acs.jmedchem.6b01870. Epub 2017 Jun 28.


DNA-Targeted Precision Medicine; Have we Been Caught Sleeping?

Reinhold WC, Thomas A, Pommier Y.

Trends Cancer. 2017 Jan;3(1):2-6. doi: 10.1016/j.trecan.2016.11.002.


Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA Phosphodiesterase 2 (Tdp2).

Wang P, Elsayed MSA, Plescia CB, Ravji A, Redon CE, Kiselev E, Marchand C, Zeleznik O, Agama K, Pommier Y, Cushman M.

J Med Chem. 2017 Apr 27;60(8):3275-3288. doi: 10.1021/acs.jmedchem.6b01565. Epub 2017 Apr 18.


The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).

Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K.

Oncotarget. 2017 May 16;8(20):33457-33474. doi: 10.18632/oncotarget.16508.


A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress.

Bruno PM, Liu Y, Park GY, Murai J, Koch CE, Eisen TJ, Pritchard JR, Pommier Y, Lippard SJ, Hemann MT.

Nat Med. 2017 Apr;23(4):461-471. doi: 10.1038/nm.4291. Epub 2017 Feb 27.


Temozolomide in the Era of Precision Medicine.

Thomas A, Tanaka M, Trepel J, Reinhold WC, Rajapakse VN, Pommier Y.

Cancer Res. 2017 Feb 15;77(4):823-826. doi: 10.1158/0008-5472.CAN-16-2983. Epub 2017 Feb 3. Review.


Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay.

Ji J, Zhang Y, Redon CE, Reinhold WC, Chen AP, Fogli LK, Holbeck SL, Parchment RE, Hollingshead M, Tomaszewski JE, Dudon Q, Pommier Y, Doroshow JH, Bonner WM.

PLoS One. 2017 Feb 3;12(2):e0171582. doi: 10.1371/journal.pone.0171582. eCollection 2017.


Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks.

Huang SN, Williams JS, Arana ME, Kunkel TA, Pommier Y.

EMBO J. 2017 Feb 1;36(3):361-373. doi: 10.15252/embj.201592426. Epub 2016 Dec 8.


The NCI-60 Methylome and Its Integration into CellMiner.

Reinhold WC, Varma S, Sunshine M, Rajapakse V, Luna A, Kohn KW, Stevenson H, Wang Y, Heyn H, Nogales V, Moran S, Goldstein DJ, Doroshow JH, Meltzer PS, Esteller M, Pommier Y.

Cancer Res. 2017 Feb 1;77(3):601-612. doi: 10.1158/0008-5472.CAN-16-0655. Epub 2016 Dec 6.


Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action.

Pommier Y, O'Connor MJ, de Bono J.

Sci Transl Med. 2016 Oct 26;8(362):362ps17. Erratum in: Sci Transl Med. 2016 Dec 7;8(368):368er7.


Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.

Pommier Y, Sun Y, Huang SN, Nitiss JL.

Nat Rev Mol Cell Biol. 2016 Nov;17(11):703-721. doi: 10.1038/nrm.2016.111. Epub 2016 Sep 21. Review.


Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR inhibition.

Murai J, Feng Y, Yu GK, Ru Y, Tang SW, Shen Y, Pommier Y.

Oncotarget. 2016 Nov 22;7(47):76534-76550. doi: 10.18632/oncotarget.12266.


Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes.

Riddell IA, Agama K, Park GY, Pommier Y, Lippard SJ.

ACS Chem Biol. 2016 Nov 18;11(11):2996-3001. Epub 2016 Oct 6.


Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer.

Mameri H, Bièche I, Meseure D, Marangoni E, Buhagiar-Labarchède G, Nicolas A, Vacher S, Onclercq-Delic R, Rajapakse V, Varma S, Reinhold WC, Pommier Y, Amor-Guéret M.

Clin Cancer Res. 2017 Apr 15;23(8):2116-2126. doi: 10.1158/1078-0432.CCR-16-0626. Epub 2016 Sep 6.


Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors.

Jdey W, Thierry S, Russo C, Devun F, Al Abo M, Noguiez-Hellin P, Sun JS, Barillot E, Zinovyev A, Kuperstein I, Pommier Y, Dutreix M.

Clin Cancer Res. 2017 Feb 15;23(4):1001-1011. doi: 10.1158/1078-0432.CCR-16-1193. Epub 2016 Aug 24.


Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage.

Rao T, Gao R, Takada S, Al Abo M, Chen X, Walters KJ, Pommier Y, Aihara H.

Nucleic Acids Res. 2016 Dec 1;44(21):10201-10215. Epub 2016 Aug 19.


Small cell lung cancer: Time to revisit DNA-damaging chemotherapy.

Thomas A, Pommier Y.

Sci Transl Med. 2016 Jul 6;8(346):346fs12. doi: 10.1126/scitranslmed.aaf6282. Review.


Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site.

Métifiot M, Johnson BC, Kiselev E, Marler L, Zhao XZ, Burke TR Jr, Marchand C, Hughes SH, Pommier Y.

Nucleic Acids Res. 2016 Aug 19;44(14):6896-906. doi: 10.1093/nar/gkw592. Epub 2016 Jul 1.


F10 cytotoxicity via topoisomerase I cleavage complex repair consistent with a unique mechanism for thymineless death.

Gmeiner WH, Gearhart PJ, Pommier Y, Nakamura J.

Future Oncol. 2016 Oct;12(19):2183-8. doi: 10.2217/fon-2016-0127. Epub 2016 Jun 22. Review. No abstract available.


Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft.

Kossmann BR, Abdelmalak M, Lopez S, Tender G, Yan C, Pommier Y, Marchand C, Ivanov I.

Bioorg Med Chem Lett. 2016 Jul 15;26(14):3232-3236. doi: 10.1016/j.bmcl.2016.05.065. Epub 2016 May 24.


Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo.

Cho JE, Huang SY, Burgers PM, Shuman S, Pommier Y, Jinks-Robertson S.

Nucleic Acids Res. 2016 Sep 19;44(16):7714-21. doi: 10.1093/nar/gkw495. Epub 2016 Jun 1.


RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals.

Ahmad M, Xue Y, Lee SK, Martindale JL, Shen W, Li W, Zou S, Ciaramella M, Debat H, Nadal M, Leng F, Zhang H, Wang Q, Siaw GE, Niu H, Pommier Y, Gorospe M, Hsieh TS, Tse-Dinh YC, Xu D, Wang W.

Nucleic Acids Res. 2016 Jul 27;44(13):6335-49. doi: 10.1093/nar/gkw508. Epub 2016 Jun 1.


Chromatin Regulators as a Guide for Cancer Treatment Choice.

Gurard-Levin ZA, Wilson LO, Pancaldi V, Postel-Vinay S, Sousa FG, Reyes C, Marangoni E, Gentien D, Valencia A, Pommier Y, Cottu P, Almouzni G.

Mol Cancer Ther. 2016 Jul;15(7):1768-77. doi: 10.1158/1535-7163.MCT-15-1008. Epub 2016 May 16.


Clinical and pharmacologic evaluation of two dosing schedules of indotecan (LMP400), a novel indenoisoquinoline, in patients with advanced solid tumors.

Kummar S, Chen A, Gutierrez M, Pfister TD, Wang L, Redon C, Bonner WM, Yutzy W, Zhang Y, Kinders RJ, Ji J, Allen D, Covey JM, Eiseman JL, Holleran JL, Beumer JH, Rubinstein L, Collins J, Tomaszewski J, Parchment R, Pommier Y, Doroshow JH.

Cancer Chemother Pharmacol. 2016 Jul;78(1):73-81. doi: 10.1007/s00280-016-2998-6. Epub 2016 May 11.


Deazaflavin Inhibitors of Tyrosyl-DNA Phosphodiesterase 2 (TDP2) Specific for the Human Enzyme and Active against Cellular TDP2.

Marchand C, Abdelmalak M, Kankanala J, Huang SY, Kiselev E, Fesen K, Kurahashi K, Sasanuma H, Takeda S, Aihara H, Wang Z, Pommier Y.

ACS Chem Biol. 2016 Jul 15;11(7):1925-33. doi: 10.1021/acschembio.5b01047. Epub 2016 May 11.


Design, Synthesis, and Biological Evaluation of Potential Prodrugs Related to the Experimental Anticancer Agent Indotecan (LMP400).

Lv PC, Elsayed MS, Agama K, Marchand C, Pommier Y, Cushman M.

J Med Chem. 2016 May 26;59(10):4890-9. doi: 10.1021/acs.jmedchem.6b00220. Epub 2016 Apr 20.


Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase I Poisons.

Beck DE, Reddy PV, Lv W, Abdelmalak M, Tender GS, Lopez S, Agama K, Marchand C, Pommier Y, Cushman M.

J Med Chem. 2016 Apr 28;59(8):3840-53. doi: 10.1021/acs.jmedchem.6b00003. Epub 2016 Apr 12.


RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription.

Baranello L, Wojtowicz D, Cui K, Devaiah BN, Chung HJ, Chan-Salis KY, Guha R, Wilson K, Zhang X, Zhang H, Piotrowski J, Thomas CJ, Singer DS, Pugh BF, Pommier Y, Przytycka TM, Kouzine F, Lewis BA, Zhao K, Levens D.

Cell. 2016 Apr 7;165(2):357-71. doi: 10.1016/j.cell.2016.02.036.


Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations.

Jensen NF, Agama K, Roy A, Smith DH, Pfister TD, Rømer MU, Zhang HL, Doroshow JH, Knudsen BR, Stenvang J, Brünner N, Pommier Y.

J Exp Clin Cancer Res. 2016 Mar 31;35:56. doi: 10.1186/s13046-016-0335-x.


Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

Shamanna RA, Lu H, Croteau DL, Arora A, Agarwal D, Ball G, Aleskandarany MA, Ellis IO, Pommier Y, Madhusudan S, Bohr VA.

Oncotarget. 2016 Mar 22;7(12):13269-84. doi: 10.18632/oncotarget.7906.


Analogs of the novel phytohormone, strigolactone, trigger apoptosis and synergize with PARP inhibitors by inducing DNA damage and inhibiting DNA repair.

Croglio MP, Haake JM, Ryan CP, Wang VS, Lapier J, Schlarbaum JP, Dayani Y, Artuso E, Prandi C, Koltai H, Agama K, Pommier Y, Chen Y, Tricoli L, LaRocque JR, Albanese C, Yarden RI.

Oncotarget. 2016 Mar 22;7(12):13984-4001. doi: 10.18632/oncotarget.7414.


Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2).

Kankanala J, Marchand C, Abdelmalak M, Aihara H, Pommier Y, Wang Z.

J Med Chem. 2016 Mar 24;59(6):2734-46. doi: 10.1021/acs.jmedchem.5b01973. Epub 2016 Mar 7.


topIb, a phylogenetic hallmark gene of Thaumarchaeota encodes a functional eukaryote-like topoisomerase IB.

Dahmane N, Gadelle D, Delmas S, Criscuolo A, Eberhard S, Desnoues N, Collin S, Zhang H, Pommier Y, Forterre P, Sezonov G.

Nucleic Acids Res. 2016 Apr 7;44(6):2795-805. doi: 10.1093/nar/gkw097. Epub 2016 Feb 22.


Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons.

Beck DE, Lv W, Abdelmalak M, Plescia CB, Agama K, Marchand C, Pommier Y, Cushman M.

Bioorg Med Chem. 2016 Apr 1;24(7):1469-79. doi: 10.1016/j.bmc.2016.02.015. Epub 2016 Feb 9.


Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization of synthesis and evaluation of antitumor properties.

Shchekotikhin AE, Dezhenkova LG, Tsvetkov VB, Luzikov YN, Volodina YL, Tatarskiy VV Jr, Kalinina AA, Treshalin MI, Treshalina HM, Romanenko VI, Kaluzhny DN, Kubbutat M, Schols D, Pommier Y, Shtil AA, Preobrazhenskaya MN.

Eur J Med Chem. 2016 Apr 13;112:114-129. doi: 10.1016/j.ejmech.2016.01.050. Epub 2016 Feb 4.


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