John Pascal

TitleAssoc Professor
InstitutionThomas Jefferson University
DepartmentBiochem & Molecular Biology
Address233 S. 10th Street
Philadelphia PA 19107
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    F32GM070151     (PASCAL, JOHN)Apr 1, 2004 - Mar 31, 2005
    NIH/NIGMS
    Protein-Protein Interactions in DNA Repair Pathways
    Role: Principal Investigator

    R01GM087282     (PASCAL, JOHN)Dec 1, 2010 - Nov 30, 2015
    NIH/NIGMS
    Structural Biochemistry of PARP-1
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Hammel M, Rashid I, Sverzhinsky A, Pourfarjam Y, Tsai MS, Ellenberger T, Pascal JM, Kim IK, Tainer JA, Tomkinson AE. An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIa within a flexible DNA repair complex. Nucleic Acids Res. 2021 01 11; 49(1):306-321. PMID: 33330937.
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    2. Genois MM, Gagné JP, Yasuhara T, Jackson J, Saxena S, Langelier MF, Ahel I, Bedford MT, Pascal JM, Vindigni A, Poirier GG, Zou L. CARM1 regulates replication fork speed and stress response by stimulating PARP1. Mol Cell. 2020 Dec 30. PMID: 33412112.
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    3. Serrano D, Cordero G, Kawamura R, Sverzhinsky A, Sarker M, Roy S, Malo C, Pascal JM, Marko JF, D'Amours D. The Smc5/6 Core Complex Is a Structure-Specific DNA Binding and Compacting Machine. Mol Cell. 2020 12 17; 80(6):1025-1038.e5. PMID: 33301731.
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    4. Rouleau-Turcotte É, Pascal JM. Bridging a DNA Break to Leave a Poly(ADP-Ribose) Mark on Chromatin. Mol Cell. 2020 11 19; 80(4):560-561. PMID: 33217315.
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    5. Matsumoto Y, Brooks RC, Sverzhinsky A, Pascal JM, Tomkinson AE. Dynamic DNA-bound PCNA complexes co-ordinate Okazaki fragment synthesis, processing and ligation. J Mol Biol. 2020 Dec 04; 432(24):166698. PMID: 33157085.
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    6. Shao Z, Lee BJ, Rouleau-Turcotte É, Langelier MF, Lin X, Estes VM, Pascal JM, Zha S. Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo. Nucleic Acids Res. 2020 09 25; 48(17):9694-9709. PMID: 32890402.
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    7. Koirala S, Klein J, Zheng Y, Glenn NO, Eisemann T, Fon Tacer K, Miller DJ, Kulak O, Lu M, Finkelstein DB, Neale G, Tillman H, Vogel P, Strand DW, Lum L, Brautigam CA, Pascal JM, Clements WK, Potts PR. Tissue-Specific Regulation of the Wnt/ß-Catenin Pathway by PAGE4 Inhibition of Tankyrase. Cell Rep. 2020 Jul 21; 32(3):107922. PMID: 32698014.
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    8. Zandarashvili L, Langelier MF, Velagapudi UK, Hancock MA, Steffen JD, Billur R, Hannan ZM, Wicks AJ, Krastev DB, Pettitt SJ, Lord CJ, Talele TT, Pascal JM, Black BE. Structural basis for allosteric PARP-1 retention on DNA breaks. Science. 2020 04 03; 368(6486). PMID: 32241924.
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    9. Manenda MS, Picard MÈ, Zhang L, Cyr N, Zhu X, Barma J, Pascal JM, Couture M, Zhang C, Shi R. Structural analyses of the Group A flavin-dependent monooxygenase PieE reveal a sliding FAD cofactor conformation bridging OUT and IN conformations. J Biol Chem. 2020 Apr 03; 295(14):4709-4722. PMID: 32111738.
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    10. Eisemann T, Pascal JM. Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity. Cell Mol Life Sci. 2020 Jan; 77(1):19-33. PMID: 31754726.
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    11. Eisemann T, Langelier MF, Pascal JM. Structural and functional analysis of parameters governing tankyrase-1 interaction with telomeric repeat-binding factor 1 and GDP-mannose dehydratase. J Biol Chem. 2019 Aug 02. PMID: 31375564.
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    12. Caron MC, Sharma AK, O'Sullivan J, Myler LR, Ferreira MT, Rodrigue A, Coulombe Y, Ethier C, Gagné JP, Langelier MF, Pascal JM, Finkelstein IJ, Hendzel MJ, Poirier GG, Masson JY. Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks. Nat Commun. 2019 Jul 04; 10(1):2954. PMID: 31273204.
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    13. Velagapudi UK, Langelier MF, Delgado-Martin C, Diolaiti ME, Bakker S, Ashworth A, Patel BA, Shao X, Pascal JM, Talele TT. Design and Synthesis of Poly(ADP-ribose) polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity. J Med Chem. 2019 May 01. PMID: 31042381.
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    14. Cohen-Armon M, Yeheskel A, Pascal JM. Signal-induced PARP1-Erk synergism mediates IEG expression. Signal Transduct Target Ther. 2019; 4:8. PMID: 30993015.
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    15. Langelier MF, Eisemann T, Riccio AA, Pascal JM. PARP family enzymes: regulation and catalysis of the poly(ADP-ribose) posttranslational modification. Curr Opin Struct Biol. 2018 12; 53:187-198. PMID: 30481609.
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    16. Pascal JM. The comings and goings of PARP-1 in response to DNA damage. DNA Repair (Amst). 2018 Aug 23. PMID: 30177435.
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    17. Gagné JP, Langelier MF, Pascal JM, Poirier GG. Hydrofluoric Acid-Based Derivatization Strategy To Profile PARP-1 ADP-Ribosylation by LC-MS/MS. J Proteome Res. 2018 Jul 06; 17(7):2542-2551. PMID: 29812941.
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    18. Langelier MF, Zandarashvili L, Aguiar PM, Black BE, Pascal JM. NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains. Nat Commun. 2018 02 27; 9(1):844. PMID: 29487285.
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    19. Karch KR, Langelier MF, Pascal JM, Garcia BA. The nucleosomal surface is the main target of histone ADP-ribosylation in response to DNA damage. Mol Biosyst. 2017 Nov 21; 13(12):2660-2671. PMID: 29058739.
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    20. Chand SN, Zarei M, Schiewer MJ, Kamath AR, Romeo C, Lal S, Cozzitorto JA, Nevler A, Scolaro L, Londin E, Jiang W, Meisner-Kober N, Pishvaian MJ, Knudsen KE, Yeo CJ, Pascal JM, Winter JM, Brody JR. Post-transcriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors. Cancer Res. 2017 Jul 07. PMID: 28687616.
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    21. Sultanov DC, Gerasimova NS, Kudryashova KS, Maluchenko NV, Kotova EY, Langelier MF, Pascal JM, Kirpichnikov MP, Feofanov AV, Studitsky VM. Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy. AIMS Genet. 2017; 4(1):21-31. PMID: 28804761.
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    22. Langelier MF, Steffen JD, Riccio AA, McCauley M, Pascal JM. Purification of DNA Damage-Dependent PARPs from E. coli for Structural and Biochemical Analysis. Methods Mol Biol. 2017; 1608:431-444. PMID: 28695525.
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    23. Lee GO, Richard SA, Kang G, Houpt ER, Seidman JC, Pendergast LL, Bhutta ZA, Ahmed T, Mduma ER, Lima AA, Bessong P, Jennifer MS, Hossain MI, Chandyo RK, Nyathi E, Lima IF, Pascal J, Soofi S, Ladaporn B, Guerrant RL, Caulfield LE, Black RE, Kosek MN. A Comparison of Diarrheal Severity Scores in the MAL-ED Multisite Community-Based Cohort Study. J Pediatr Gastroenterol Nutr. 2016 11; 63(5):466-473. PMID: 27347723.
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    24. Jeronimo C, Langelier MF, Bataille AR, Pascal JM, Pugh BF, Robert F. Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo. Mol Cell. 2016 Nov 03; 64(3):455-466. PMID: 27773677.
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    25. Eisemann T, McCauley M, Langelier MF, Gupta K, Roy S, Van Duyne GD, Pascal JM. Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification. Structure. 2016 Oct 4; 24(10):1679-1692. PMID: 27594684.
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    26. Steffen JD, McCauley MM, Pascal JM. Fluorescent sensors of PARP-1 structural dynamics and allosteric regulation in response to DNA damage. Nucleic Acids Res. 2016 Nov 16; 44(20):9771-9783. PMID: 27530425.
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    27. Riccio AA, McCauley M, Langelier MF, Pascal JM. Tankyrase Sterile a Motif Domain Polymerization Is Required for Its Role in Wnt Signaling. Structure. 2016 Sep 6; 24(9):1573-81. PMID: 27499439.
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    28. Riccio AA, Cingolani G, Pascal JM. PARP-2 domain requirements for DNA damage-dependent activation and localization to sites of DNA damage. Nucleic Acids Res. 2016 Feb 29; 44(4):1691-702. PMID: 26704974.
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    29. Eustermann S, Wu WF, Langelier MF, Yang JC, Easton LE, Riccio AA, Pascal JM, Neuhaus D. Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1. Mol Cell. 2015 Dec 3; 60(5):742-54. PMID: 26626479.
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    30. Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD, Karch KR, McCauley M, Steffen JD, Black BE, Pascal JM. PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain. Mol Cell. 2015 Dec 3; 60(5):755-68. PMID: 26626480.
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    31. Chan TO, Zhang J, Tiegs BC, Blumhof B, Yan L, Keny N, Penny M, Li X, Pascal JM, Armen RS, Rodeck U, Penn RB. Akt kinase C-terminal modifications control activation loop dephosphorylation and enhance insulin response. Biochem J. 2015 Oct 1; 471(1):37-51. PMID: 26201515.
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    32. Pascal JM, Ellenberger T. The rise and fall of poly(ADP-ribose): An enzymatic perspective. DNA Repair (Amst). 2015 Aug; 32:10-6. PMID: 25963443.
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    33. Gagné JP, Ethier C, Defoy D, Bourassa S, Langelier MF, Riccio AA, Pascal JM, Moon KM, Foster LJ, Ning Z, Figeys D, Droit A, Poirier GG. Quantitative site-specific ADP-ribosylation profiling of DNA-dependent PARPs. DNA Repair (Amst). 2015 Jun; 30:68-79. PMID: 25800440.
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    34. Zhang M, Meng XY, Cui M, Pascal JM, Logothetis DE, Zhang JF. Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex. Nat Chem Biol. 2014 Sep; 10(9):753-9. PMID: 25108821.
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    35. Patel MR, Bhatt A, Steffen JD, Chergui A, Murai J, Pommier Y, Pascal JM, Trombetta LD, Fronczek FR, Talele TT. Discovery and Structure-Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors. J Med Chem. 2014 Jul 10; 57(13):5579-601. PMID: 24922587.
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    36. Langelier MF, Riccio AA, Pascal JM. PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1. Nucleic Acids Res. 2014 Aug 1; 42(12):7762-75. PMID: 24928857.
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    37. Steffen JD, Brody JR, Armen RS, Pascal JM. Structural Implications for Selective Targeting of PARPs. Front Oncol. 2013; 3:301. PMID: 24392349.
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    38. Steffen JD, Tholey RM, Langelier MF, Planck JL, Schiewer MJ, Lal S, Bildzukewicz NA, Yeo CJ, Knudsen KE, Brody JR, Pascal JM. Targeting PARP-1 Allosteric Regulation Offers Therapeutic Potential against Cancer. Cancer Res. 2014 Jan 1; 74(1):31-7. PMID: 24189460.
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    39. Steffen JD, Pascal JM. New players to the field of ADP-ribosylation make the final cut. EMBO J. 2013 May 2; 32(9):1205-7. PMID: 23572078.
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    40. Zhang M, Pascal JM, Zhang JF. Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation. Proc Natl Acad Sci U S A. 2013 Mar 19; 110(12):4828-33. PMID: 23487779.
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    41. Karlberg T, Langelier MF, Pascal JM, Schüler H. Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling. Mol Aspects Med. 2013 Dec; 34(6):1088-108. PMID: 23458732.
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    42. Langelier MF, Pascal JM. PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis. Curr Opin Struct Biol. 2013 Feb; 23(1):134-43. PMID: 23333033.
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    43. Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, Liu F, Planck JL, Ravindranathan P, Chinnaiyan AM, McCue P, Gomella LG, Raj GV, Dicker AP, Brody JR, Pascal JM, Centenera MM, Butler LM, Tilley WD, Feng FY, Knudsen KE. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2012 Dec; 2(12):1134-49. PMID: 22993403.
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    44. Langelier MF, Planck JL, Roy S, Pascal JM. Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1. Science. 2012 May 11; 336(6082):728-32. PMID: 22582261.
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    45. Zhang M, Abrams C, Wang L, Gizzi A, He L, Lin R, Chen Y, Loll PJ, Pascal JM, Zhang JF. Structural basis for calmodulin as a dynamic calcium sensor. Structure. 2012 May 9; 20(5):911-23. PMID: 22579256.
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    46. Chan TO, Pascal JM, Armen RS, Rodeck U. Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases. Cell Cycle. 2012 Feb 1; 11(3):475-8. PMID: 22262182.
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    47. Zhang M, Pascal JM, Schumann M, Armen RS, Zhang JF. Identification of the functional binding pocket for compounds targeting small-conductance Ca²?-activated potassium channels. Nat Commun. 2012; 3:1021. PMID: 22929778.
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    48. Liu C, Sanders JM, Pascal JM, Hou YM. Adaptation to tRNA acceptor stem structure by flexible adjustment in the catalytic domain of class I tRNA synthetases. RNA. 2012 Feb; 18(2):213-21. PMID: 22184460.
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    49. Chan TO, Zhang J, Rodeck U, Pascal JM, Armen RS, Spring M, Dumitru CD, Myers V, Li X, Cheung JY, Feldman AM. Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity. Proc Natl Acad Sci U S A. 2011 Nov 15; 108(46):E1120-7. PMID: 22031698.
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    50. Langelier MF, Planck JL, Roy S, Pascal JM. Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1) zinc fingers bound to DNA: structural and functional insights into DNA-dependent PARP-1 activity. J Biol Chem. 2011 Mar 25; 286(12):10690-701. PMID: 21233213.
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    51. Langelier MF, Planck JL, Servent KM, Pascal JM. Purification of human PARP-1 and PARP-1 domains from Escherichia coli for structural and biochemical analysis. Methods Mol Biol. 2011; 780:209-26. PMID: 21870263.
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    52. Langelier MF, Ruhl DD, Planck JL, Kraus WL, Pascal JM. The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP-1) functions in both DNA-dependent poly(ADP-ribose) synthesis activity and chromatin compaction. J Biol Chem. 2010 Jun 11; 285(24):18877-87. PMID: 20388712.
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    53. Song W, Pascal JM, Ellenberger T, Tomkinson AE. The DNA binding domain of human DNA ligase I interacts with both nicked DNA and the DNA sliding clamps, PCNA and hRad9-hRad1-hHus1. DNA Repair (Amst). 2009 Aug 6; 8(8):912-9. PMID: 19523882.
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    54. Pascal JM. DNA and RNA ligases: structural variations and shared mechanisms. Curr Opin Struct Biol. 2008 Feb; 18(1):96-105. PMID: 18262407.
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    55. Langelier MF, Servent KM, Rogers EE, Pascal JM. A third zinc-binding domain of human poly(ADP-ribose) polymerase-1 coordinates DNA-dependent enzyme activation. J Biol Chem. 2008 Feb 15; 283(7):4105-14. PMID: 18055453.
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    56. Pascal JM, Ellenberger T. RNA ligase does the AMP shuffle. Nat Struct Mol Biol. 2006 Nov; 13(11):950-1. PMID: 17082787.
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    57. Pascal JM, Tsodikov OV, Hura GL, Song W, Cotner EA, Classen S, Tomkinson AE, Tainer JA, Ellenberger T. A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA. Mol Cell. 2006 Oct 20; 24(2):279-91. PMID: 17052461.
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    58. Tomkinson AE, Vijayakumar S, Pascal JM, Ellenberger T. DNA ligases: structure, reaction mechanism, and function. Chem Rev. 2006 Feb; 106(2):687-99. PMID: 16464020.
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    59. Chen X, Pascal J, Vijayakumar S, Wilson GM, Ellenberger T, Tomkinson AE. Human DNA ligases I, III, and IV-purification and new specific assays for these enzymes. Methods Enzymol. 2006; 409:39-52. PMID: 16793394.
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    60. Pascal JM, O'Brien PJ, Tomkinson AE, Ellenberger T. Human DNA ligase I completely encircles and partially unwinds nicked DNA. Nature. 2004 Nov 25; 432(7016):473-8. PMID: 15565146.
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    61. Pascal JM, Hart PJ, Hecht NB, Robertus JD. Crystal structure of TB-RBP, a novel RNA-binding and regulating protein. J Mol Biol. 2002 Jun 21; 319(5):1049-57. PMID: 12079346.
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