STEWART H SHUMAN

Summary

Affiliation: Memorial Sloan-Kettering Cancer Center
Country: USA

Publications

  1. pmc RNA triphosphatase is essential in Schizosaccharomyces pombe and Candida albicans
    Y Pei
    Molecular Biology and Cell Biology Programs, Sloan Kettering Institute, New York, NY 10021, USA
    BMC Microbiol 1:29. 2001
  2. ncbi request reprint An ATPase component of the transcription elongation complex is required for factor-dependent transcription termination by vaccinia RNA polymerase
    L Deng
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 271:29386-92. 1996
  3. pmc Substrate specificity and mutational analysis of Kluyveromyces lactis gamma-toxin, a eukaryal tRNA anticodon nuclease
    Ruchi Jain
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 17:1336-43. 2011
  4. ncbi request reprint Bacterial DNA repair by non-homologous end joining
    Stewart Shuman
    Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    Nat Rev Microbiol 5:852-61. 2007
  5. ncbi request reprint Transcriptional networking cap-tures the 7SK RNA 5'-gamma-methyltransferase
    Stewart Shuman
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Mol Cell 27:517-9. 2007
  6. pmc DNA ligases: progress and prospects
    Stewart Shuman
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    J Biol Chem 284:17365-9. 2009
  7. ncbi request reprint Interactions between fission yeast Cdk9, its cyclin partner Pch1, and mRNA capping enzyme Pct1 suggest an elongation checkpoint for mRNA quality control
    Yi Pei
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:7180-8. 2003
  8. ncbi request reprint Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 protein kinase: Spt5 phosphorylation, autophosphorylation, and mutational analysis
    Yi Pei
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:43346-56. 2003
  9. pmc Biochemical and genetic analysis of RNA cap guanine-N2 methyltransferases from Giardia lamblia and Schizosaccharomyces pombe
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Nucleic Acids Res 35:1411-20. 2007
  10. pmc Separable functions of the fission yeast Spt5 carboxyl-terminal domain (CTD) in capping enzyme binding and transcription elongation overlap with those of the RNA polymerase II CTD
    Susanne Schneider
    Graduate Program in Molecular Biology, Weill Cornell Medical College, New York, New York 10065, USA
    Mol Cell Biol 30:2353-64. 2010

Research Grants

  1. Viral and Bacterial DNA Ligases
    STEWART H SHUMAN; Fiscal Year: 2010
  2. Viral RNA Modifying Enzymes
    STEWART H SHUMAN; Fiscal Year: 2010
  3. mRNA Capping Enzymes
    STEWART H SHUMAN; Fiscal Year: 2010
  4. Viral RNA Modifying Enzymes
    Stewart Shuman; Fiscal Year: 2005
  5. Chlorella Virus DNA Ligase: Structure and Mechanism
    Stewart Shuman; Fiscal Year: 2004
  6. Novel Targets for Treatment of Smallpox
    Stewart Shuman; Fiscal Year: 2003
  7. MRNA CAPPING ENZYME
    Stewart Shuman; Fiscal Year: 2006
  8. Viral and Bacterial DNA Ligases
    Stewart Shuman; Fiscal Year: 2009
  9. mRNA Capping Enzymes
    Stewart Shuman; Fiscal Year: 2009
  10. Viral RNA Modifying Enzymes
    Stewart Shuman; Fiscal Year: 2009

Collaborators

  • Beate Schwer
  • Liang Deng
  • Feng Gao
  • Michael S Glickman
  • Robert P Fisher
  • Zhijian Chen
  • Michael Pirrung
  • Donald F Smee
  • Eric S Miller
  • Hisashi Koiwa
  • Stephane Hausmann
  • Hui Zhu
  • Delphine Benarroch
  • Yi Pei
  • Li Kai Wang
  • Pravin A Nair
  • Christopher D Lima
  • Jayakrishnan Nandakumar
  • Sushuang Zheng
  • Krishna Murari Sinha
  • Paul Smith
  • Carme Fabrega
  • Lyudmila Yakovleva
  • Chunling Gong
  • Verl Sriskanda
  • Susanne Schneider
  • Jideofor Aniukwu
  • Mark Odell
  • Ruchi Jain
  • Alexandra Martins
  • Andrea Piserchio
  • Jonathan Chang
  • Ligeng Tian
  • C Kiong Ho
  • Agnidipta Ghosh
  • Niroshika Keppetipola
  • Sidney M Hecht
  • Vincent Shen
  • Nayanendu Saha
  • Berit Olsen Krogh
  • Y Pei
  • Julien Gros
  • Anupam K Chakravarty
  • Michael G Poulos
  • Ranajeet Ghose
  • Janusz Stepinski
  • Edward Darzynkiewicz
  • Marzena Jankowska-Anyszka
  • Zhicheng R Qiu
  • Mihaela Carmen Unciuleac
  • Shengxi Chen
  • Alejandro Ramirez
  • Hongyan Du
  • Courtney Stamour
  • Juliet Singer
  • Selena Granitto
  • Michael Hampsey
  • Heidi G Elmendorf
  • Stewart W Schneller
  • Nicolas C Stephanou
  • Shankarling Krishnamurthy
  • Matthew Witmer
  • Paola Bongiorno
  • Melissa A Altura
  • Steven M Singer
  • Hediye Erdjument-Bromage
  • Shenmin Yin
  • Govind P Kalena
  • Donald M Jerina
  • Christopher D Claeboe
  • Marianna Teplova
  • Heiko Kroth
  • Jane M Sayer
  • Lucy Malinina
  • J Saiz

Detail Information

Publications65

  1. pmc RNA triphosphatase is essential in Schizosaccharomyces pombe and Candida albicans
    Y Pei
    Molecular Biology and Cell Biology Programs, Sloan Kettering Institute, New York, NY 10021, USA
    BMC Microbiol 1:29. 2001
    ....
  2. ncbi request reprint An ATPase component of the transcription elongation complex is required for factor-dependent transcription termination by vaccinia RNA polymerase
    L Deng
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 271:29386-92. 1996
    ..We propose that factor X, which has an associated DNA-dependent ATPase activity, mediates the requirement for ATP hydrolysis during transcription termination...
  3. pmc Substrate specificity and mutational analysis of Kluyveromyces lactis gamma-toxin, a eukaryal tRNA anticodon nuclease
    Ruchi Jain
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 17:1336-43. 2011
    ..By analogy to other endoribonucleases, we speculate that γ-toxin drives transesterification by general acid-base catalysis (via His209 and Glu9) and transition-state stabilization (via Arg151)...
  4. ncbi request reprint Bacterial DNA repair by non-homologous end joining
    Stewart Shuman
    Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
    Nat Rev Microbiol 5:852-61. 2007
    ..Although still a young field, bacterial NHEJ promises to teach us a great deal about the nexus of DNA repair and bacterial pathogenesis...
  5. ncbi request reprint Transcriptional networking cap-tures the 7SK RNA 5'-gamma-methyltransferase
    Stewart Shuman
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Mol Cell 27:517-9. 2007
    ..In a recent issue of Molecular Cell, Jeronimo et al. (2007) identify BCDIN3, a Cdk9-associated protein, as the enzyme that forms the distinctive gamma-methylphosphate cap structure of 7SK, a noncoding RNA that regulates Cdk9 activity...
  6. pmc DNA ligases: progress and prospects
    Stewart Shuman
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    J Biol Chem 284:17365-9. 2009
    ....
  7. ncbi request reprint Interactions between fission yeast Cdk9, its cyclin partner Pch1, and mRNA capping enzyme Pct1 suggest an elongation checkpoint for mRNA quality control
    Yi Pei
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:7180-8. 2003
    ..This elongation checkpoint may avoid wasteful rounds of transcription of uncapped pre-mRNAs...
  8. ncbi request reprint Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 protein kinase: Spt5 phosphorylation, autophosphorylation, and mutational analysis
    Yi Pei
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:43346-56. 2003
    ....
  9. pmc Biochemical and genetic analysis of RNA cap guanine-N2 methyltransferases from Giardia lamblia and Schizosaccharomyces pombe
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Nucleic Acids Res 35:1411-20. 2007
    ..Deletion of the pcm1(+) gene was lethal, as were missense mutations in the Pcm1 active site. Thus, whereas m(7)G caps are essential in both S. pombe and S. cerevisiae, m(2,2,7)G caps are not...
  10. pmc Separable functions of the fission yeast Spt5 carboxyl-terminal domain (CTD) in capping enzyme binding and transcription elongation overlap with those of the RNA polymerase II CTD
    Susanne Schneider
    Graduate Program in Molecular Biology, Weill Cornell Medical College, New York, New York 10065, USA
    Mol Cell Biol 30:2353-64. 2010
    ..Viability of yeast cells bearing both Spt5 CTD T1A and Pol II CTD S2A mutations heralds that the Cdk9 kinase has an essential target other than Spt5 and Pol II CTD-Ser2...
  11. ncbi request reprint Interactions between fission yeast mRNA capping enzymes and elongation factor Spt5
    Yi Pei
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 277:19639-48. 2002
    ..pombe Spt4 via a central domain distinct from the Spt5 CTD. We suggest that Spt5-induced arrest of elongation at promoter proximal positions ensures a temporal window for recruitment of the capping enzymes...
  12. pmc Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells
    Liang Deng
    Molecular Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10021, USA
    J Virol 80:9977-87. 2006
    ..Vaccinia virus infection of primary LCs strongly inhibited their capacity for antigen-specific activation of T cells. Our results highlight suppression of the skin immune response as a feature of orthopoxvirus infection...
  13. ncbi request reprint Structure of an mRNA capping enzyme bound to the phosphorylated carboxy-terminal domain of RNA polymerase II
    Carme Fabrega
    Biochemistry Department, Structural Biology Program, Weill Medical College of Cornell University, New York, NY 10021, USA
    Mol Cell 11:1549-61. 2003
    ..A binding site for the RNA triphosphatase component of the capping apparatus was also uncovered within the Cgt1 OB domain...
  14. pmc Analysis of the DNA joining repertoire of Chlorella virus DNA ligase and a new crystal structure of the ligase-adenylate intermediate
    Mark Odell
    Sloan Kettering Institute, New York, NY 10021, USA
    Nucleic Acids Res 31:5090-100. 2003
    ..e. by enhancing some components of the functional repertoire of the ancestral ligase while disabling others...
  15. pmc Cyclin-dependent kinase 9 (Cdk9) of fission yeast is activated by the CDK-activating kinase Csk1, overlaps functionally with the TFIIH-associated kinase Mcs6, and associates with the mRNA cap methyltransferase Pcm1 in vivo
    Yi Pei
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY
    Mol Cell Biol 26:777-88. 2006
    ..Together, the data support a proposed model whereby Cdk9/Pch1-the third essential CDK-cyclin complex described in fission yeast-helps to target the capping apparatus to the transcriptional elongation complex...
  16. pmc Vaccinia virus subverts a mitochondrial antiviral signaling protein-dependent innate immune response in keratinocytes through its double-stranded RNA binding protein, E3
    Liang Deng
    Department of Medicine, Dermatology Service, Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Virol 82:10735-46. 2008
    ..IRF3 phosphorylation is induced in keratinocytes infected with DeltaE3L, an event that depends on MAVS. The response of keratinocytes to DeltaE3L is unaffected by genetic ablation of Toll-like receptor 3 (TLR3), TRIF, TLR9, and MyD88...
  17. pmc The structure of Fcp1, an essential RNA polymerase II CTD phosphatase
    Agnidipta Ghosh
    Structural Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Mol Cell 32:478-90. 2008
    ..The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site...
  18. ncbi request reprint Role of nucleotidyl transferase motif V in strand joining by chlorella virus DNA ligase
    Verl Sriskanda
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 277:9661-7. 2002
    ..Gel-shift analysis showed that the Lys(188) mutants bound stably to DNA-adenylate. We infer that Lys(188) is involved in the chemical step of phosphodiester bond formation...
  19. ncbi request reprint Structural basis for nick recognition by a minimal pluripotent DNA ligase
    Pravin A Nair
    Molecular Biology and Structural Biology Programs, Sloan Kettering Institute, New York, New York 10021, USA
    Nat Struct Mol Biol 14:770-8. 2007
    ..Addition of a divalent cation triggered nick sealing in crystallo, establishing that the nick complex is a bona fide intermediate in the DNA repair pathway...
  20. ncbi request reprint RNA ligase structures reveal the basis for RNA specificity and conformational changes that drive ligation forward
    Jayakrishnan Nandakumar
    Structural Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Cell 127:71-84. 2006
    ..Mutational analysis and comparison of nick-bound structures of Rnl2 and human DNA ligase I highlight common and divergent themes of substrate recognition that can explain their specialization for RNA versus DNA repair...
  21. doi request reprint Characterization of a trifunctional mimivirus mRNA capping enzyme and crystal structure of the RNA triphosphatase domain
    Delphine Benarroch
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Structure 16:501-12. 2008
    ..The mimivirus TTM-type RTPase-GTase fusion resembles the capping enzymes of amoebae, providing evidence that the ancestral large DNA virus acquired its capping enzyme from a unicellular host...
  22. ncbi request reprint Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate
    Jayakrishnan Nandakumar
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Mol Cell 26:257-71. 2007
    ..Large protein domain movements and remodeling of the active site orchestrate progression through the three chemical steps of the ligation reaction. The structure inspires a strategy for inhibitor design...
  23. ncbi request reprint Characterization of the CTD phosphatase Fcp1 from fission yeast. Preferential dephosphorylation of serine 2 versus serine 5
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 277:21213-20. 2002
    ....
  24. ncbi request reprint Defining the active site of Schizosaccharomyces pombe C-terminal domain phosphatase Fcp1
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:13627-32. 2003
    ....
  25. pmc Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing
    Jonathan Chang
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 16:1018-31. 2010
    ..Mud2 mutational effects in the swm2Delta background paralleled those for mud1Delta. The requirements for Mud2 function are apparently more stringent when yeast cells lack TMG caps than when they lack Mud1 or Swm2...
  26. pmc Characterization of the Schizosaccharomyces pombe Spt5-Spt4 complex
    Beate Schwer
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065, USA
    RNA 15:1241-50. 2009
    ..pombe growth, but only when Spt4 was present. Synthetic lethality of the spt5(1-835) spt4Delta double mutant at 34 degrees C suggests that interaction of Spt4 with the central domain of Spt5 overlaps functionally with the Spt5 CTD...
  27. pmc Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical coupling
    Krishna Murari Sinha
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    Biochemistry 48:4019-30. 2009
    ....
  28. pmc Characterization of Agrobacterium tumefaciens DNA ligases C and D
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Nucleic Acids Res 35:3631-45. 2007
    ..Ligation at DNA double-strand breaks in vitro by LigD2, LigC2 and LigC3 is stimulated by bacterial Ku, consistent with their proposed function in NHEJ...
  29. pmc Structure of bacterial LigD 3'-phosphoesterase unveils a DNA repair superfamily
    Pravin A Nair
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:12822-7. 2010
    ..The PE active site and mechanism are unique vis à vis other end-healing enzymes. We find PE homologs in archaeal and eukaryal proteomes, signifying that PEs comprise a DNA repair superfamily...
  30. ncbi request reprint Conserved residues in domain Ia are required for the reaction of Escherichia coli DNA ligase with NAD+
    Verl Sriskanda
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 277:9695-700. 2002
    ..We suggest that these five side chains comprise a binding site for the nicotinamide mononucleotide moiety of NAD(+). Structure-activity relationships were clarified by conservative substitutions...
  31. pmc Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase
    Sushuang Zheng
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 14:696-705. 2008
    ..The structure-function data yield a coherent picture of the vaccinia cap methyltransferase active site and the determinants of substrate specificity and affinity...
  32. pmc Chemical and traditional mutagenesis of vaccinia DNA topoisomerase provides insights to cleavage site recognition and transesterification chemistry
    Lyudmila Yakovleva
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    J Biol Chem 283:16093-103. 2008
    ..These results underscore functional redundancy at the TopIB-DNA interface...
  33. pmc Structure-guided mutational analysis of the OB, HhH, and BRCT domains of Escherichia coli DNA ligase
    Li Kai Wang
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 283:23343-52. 2008
    ..We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation...
  34. pmc Cap analog substrates reveal three clades of cap guanine-N2 methyltransferases with distinct methyl acceptor specificities
    Delphine Benarroch
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 16:211-20. 2010
    ..The relaxed cap specificity of MimiTgs is revealed at alkaline pH. Our findings highlight both stark and subtle differences in acceptor specificity and reaction outcomes among Tgs family members...
  35. pmc Mutational analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase reveals essential contributions of the N-terminal peptide that closes over the active site
    Sushuang Zheng
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    RNA 14:2297-304. 2008
    ....
  36. pmc Solution NMR studies of Chlorella virus DNA ligase-adenylate
    Andrea Piserchio
    Department of Chemistry, The City College of New York, New York, NY 10031, USA
    J Mol Biol 395:291-308. 2010
    ..We hypothesize that phosphate anion mimics some of the conformational transitions that occur when ligase-adenylate interacts with the nick 5'-phosphate...
  37. pmc Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA)
    Li Kai Wang
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    J Biol Chem 284:8486-94. 2009
    ....
  38. pmc AdnAB: a new DSB-resecting motor-nuclease from mycobacteria
    Krishna Murari Sinha
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    Genes Dev 23:1423-37. 2009
    ..AdnAB is a novel signature of the Actinomycetales taxon. Mycobacteria are exceptional in that they encode both AdnAB and RecBCD, suggesting the existence of alternative end-resecting motor-nuclease complexes...
  39. ncbi request reprint An encephalitozoon cuniculi ortholog of the RNA polymerase II carboxyl-terminal domain (CTD) serine phosphatase Fcp1
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    Biochemistry 43:7111-20. 2004
    ..We exploit synthetic CTD Ser2-PO(4) and Ser5-PO(4) peptides to define minimized substrates for EcFcp1 and to illuminate the importance of CTD primary structure in Ser2 and Ser5 phosphatase activity...
  40. pmc Characterization of a mimivirus RNA cap guanine-N2 methyltransferase
    Delphine Benarroch
    Sloan Kettering Institute, New York, New York 10065, USA
    RNA 15:666-74. 2009
    ..Our results hint that DMG caps can satisfy many of the functions of TMG caps in vivo. We speculate that DMG capping of mimivirus mRNAs might favor viral protein synthesis in the infected host...
  41. ncbi request reprint The polynucleotide ligase and RNA capping enzyme superfamily of covalent nucleotidyltransferases
    Stewart Shuman
    Molecular Biology and Structural Biology Programs, Sloan Kettering Institute for Cancer Research, New York, New York 10021, USA
    Curr Opin Struct Biol 14:757-64. 2004
    ..The first crystal structure of an RNA ligase suggests that contemporary DNA ligases, RNA ligases and RNA capping enzymes evolved by fusion of ancillary effector domains to an ancestral catalytic module involved in RNA repair...
  42. pmc A poxvirus-like type IB topoisomerase family in bacteria
    Berit Olsen Krogh
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 99:1853-8. 2002
    ..Remarkably, bacteria that possess topoisomerase IB appear to lack DNA topoisomerase III...
  43. ncbi request reprint Yeast-like mRNA capping apparatus in Giardia lamblia
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:12077-86. 2005
    ..These findings place fungi, protozoa, and red algae in a common lineage distinct from that of metazoa and plants...
  44. ncbi request reprint A primer-dependent polymerase function of pseudomonas aeruginosa ATP-dependent DNA ligase (LigD)
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:418-27. 2005
    ..We speculate that polymerase activity is relevant to LigD function in nonhomologous end-joining...
  45. ncbi request reprint Characterization of polynucleotide kinase/phosphatase enzymes from Mycobacteriophages omega and Cjw1 and vibriophage KVP40
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 279:26358-69. 2004
    ..A supportive correlation is that Omega and Cjw1, which are distinguished from other mycobacteriophages by their possession of a Pnkp enzyme, are also unique among the mycobacteriophages in their specification of putative RNA ligases...
  46. ncbi request reprint Structure and mechanism of mRNA cap (guanine-N7) methyltransferase
    Carme Fabrega
    Biochemistry Department, Structural Biology Program, Weill Medical College, Cornell University, New York, NY 10021, USA
    Mol Cell 13:77-89. 2004
    ..The enzyme-ligand structures, together with new mutational data, fully account for the biochemical specificity of the cap guanine-N7 methylation reaction, an essential and defining step of eukaryotic mRNA synthesis...
  47. ncbi request reprint Schizosaccharomyces pombe carboxyl-terminal domain (CTD) phosphatase Fcp1: distributive mechanism, minimal CTD substrate, and active site mapping
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 279:10892-900. 2004
    ..Our results, together with previous mutational studies, highlight a constellation of 11 amino acids that are conserved in all Fcp1 orthologs and likely comprise the active site...
  48. ncbi request reprint Site-specific DNA transesterification by vaccinia topoisomerase: effects of benzo[alpha]pyrene-dA, 8-oxoguanine, 8-oxoadenine and 2-aminopurine modifications
    Lyudmila Yakovleva
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    J Biol Chem 278:42170-7. 2003
    ..These findings illuminate the functional interface of vaccinia topoisomerase with the DNA major groove...
  49. pmc Yeast-based genetic system for functional analysis of poxvirus mRNA cap methyltransferase
    Nayanendu Saha
    Department of Microbiology and Immunology, Weill Medical College of Cornell University Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Virol 77:7300-7. 2003
    ..Studies of recombinant proteins show that the lethal vD1-C mutations do not preclude heterodimerization with vD12 but either eliminate or reduce cap methyltransferase activity in vitro...
  50. ncbi request reprint Mutational analysis of bacteriophage T4 RNA ligase 1. Different functional groups are required for the nucleotidyl transfer and phosphodiester bond formation steps of the ligation reaction
    Li Kai Wang
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 278:29454-62. 2003
    ..Arg-54 and Lys-119 are thereby implicated as specific catalysts of the RNA adenylation reaction (step 2) of the ligation pathway...
  51. pmc Mapping the triphosphatase active site of baculovirus mRNA capping enzyme LEF4 and evidence for a two-metal mechanism
    Alexandra Martins
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Nucleic Acids Res 31:1455-63. 2003
    ..Synergistic activation of the LEF4 triphosphatase by manganese and magnesium suggests a two-metal mechanism of gamma phosphate hydrolysis...
  52. ncbi request reprint Specificity and mechanism of RNA cap guanine-N2 methyltransferase (Tgs1)
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:4021-4. 2005
    ..We conclude that Tgs1 is guanine-specific, that N7 methylation must precede N2 methylation, that Tgs1 acts via a distributive mechanism, and that the chemical steps of TMG synthesis do not require input from RNA or protein cofactors...
  53. ncbi request reprint Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA)
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:12137-44. 2005
    ....
  54. pmc Bacteriophage T4 RNA ligase 2 (gp24.1) exemplifies a family of RNA ligases found in all phylogenetic domains
    C Kiong Ho
    Molecular Biology Program, The Sloan Kettering Institute, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 99:12709-14. 2002
    ..These findings have implications for the evolution of covalent nucleotidyl transferases and virus-host dynamics based on RNA restriction and repair...
  55. ncbi request reprint Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase C
    Chunling Gong
    Immunology and Molecular Biology Programs, Sloan Kettering Institute, and Division of Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nat Struct Mol Biol 12:304-12. 2005
    ..Another ATP-dependent DNA ligase (LigC) provides a backup mechanism for LigD-independent error-prone repair of blunt-end DSBs. We speculate that NHEJ allows mycobacteria to evade genotoxic host defense...
  56. ncbi request reprint Essential constituents of the 3'-phosphoesterase domain of bacterial DNA ligase D, a nonhomologous end-joining enzyme
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:33707-15. 2005
    ..These constellations of critical residues are unique to LigD-like proteins, which we propose comprise a new bifunctional phosphoesterase family...
  57. pmc Structure-function analysis of Plasmodium RNA triphosphatase and description of a triphosphate tunnel metalloenzyme superfamily that includes Cet1-like RNA triphosphatases and CYTH proteins
    Chunling Gong
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    RNA 12:1468-74. 2006
    ..They likely evolved by incremental changes in an ancestral tunnel enzyme that conferred specificity for RNA 5'-end processing...
  58. ncbi request reprint Different strategies for carboxyl-terminal domain (CTD) recognition by serine 5-specific CTD phosphatases
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    J Biol Chem 280:37681-8. 2005
    ..We surmise that the reading of the CTD code does not obey uniform rules with respect to the location and phasing of specificity determinants. Thus, CTD code, like the CTD structure, is plastic...
  59. pmc Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide kinase-phosphatase
    Niroshika Keppetipola
    Molecular Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10021, USA
    RNA 12:73-82. 2006
    ..Deletion analysis defined an autonomous phosphatase domain, CthPnkp-(171-424)...
  60. pmc Atomic structure and nonhomologous end-joining function of the polymerase component of bacterial DNA ligase D
    Hui Zhu
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:1711-6. 2006
    ..Thus, LigD Pol is a direct catalyst of mutagenic nonhomologous end-joining in vivo. Our studies underscore a previously uncharacterized role for the primase-like polymerase family in DNA repair...
  61. ncbi request reprint Genetic analysis of poxvirus mRNA cap methyltransferase: suppression of conditional mutations in the stimulatory D12 subunit by second-site mutations in the catalytic D1 subunit
    Beate Schwer
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Virology 352:145-56. 2006
    ....
  62. ncbi request reprint Characterization of mimivirus NAD+-dependent DNA ligase
    Delphine Benarroch
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Virology 353:133-43. 2006
    ..We speculate that the dissemination of NAD+-dependent ligase from bacterium to eukaryotic virus might have occurred within an amoebal host...
  63. pmc The pathways and outcomes of mycobacterial NHEJ depend on the structure of the broken DNA ends
    Jideofor Aniukwu
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 22:512-27. 2008
    ..We conclude that the mechanisms of mycobacterial NHEJ are many and the outcomes depend on the initial structures of the DSBs and the available ensemble of end-processing and end-sealing components, which are not limited to Ku and LigD...
  64. ncbi request reprint Guarding the genome: electrostatic repulsion of water by DNA suppresses a potent nuclease activity of topoisomerase IB
    Ligeng Tian
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021, USA
    Mol Cell 12:199-208. 2003
    ..These findings expose an Achilles' heel of topoisomerases as guardians of the genome, and they have broad implications for understanding enzymatic phosphoryl transfer...
  65. ncbi request reprint Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis
    Stephane Hausmann
    Molecular Biology and Structural Biology Programs, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:20404-12. 2005
    ..Amino acids Lys-54, Asp-70, Asp-78, and Asp-94, which comprise the AdoMet-binding site, and Phe-141, which contacts the cap guanosine, are essential for cap methyltransferase activity in vitro...

Research Grants65

  1. Viral and Bacterial DNA Ligases
    STEWART H SHUMAN; Fiscal Year: 2010
    ....
  2. Viral RNA Modifying Enzymes
    STEWART H SHUMAN; Fiscal Year: 2010
    ..Poxvirus cap methyltransferase is also distinguished from the human counterpart by its reliance on a unique virus-encoded regulatory subunit. ..
  3. mRNA Capping Enzymes
    STEWART H SHUMAN; Fiscal Year: 2010
    ..We characterized Tgs1 and Tgs2 as cap-specific guanine-N2 methyltransferases. We aim to elucidate their mechanism and structure. ..
  4. Viral RNA Modifying Enzymes
    Stewart Shuman; Fiscal Year: 2005
    ..This component of the project will illuminate the structural basis for protein-catalyzed RNA recombination/repair events and evolutionary transitions from RNA-world to DNA-world enzymology. ..
  5. Chlorella Virus DNA Ligase: Structure and Mechanism
    Stewart Shuman; Fiscal Year: 2004
    ..The findings will provide new insights into DNA damage recognition - an issue relevant to human health in light of the emerging genetic connections between DNA repair pathways and human cancer predisposition. ..
  6. Novel Targets for Treatment of Smallpox
    Stewart Shuman; Fiscal Year: 2003
    ....
  7. MRNA CAPPING ENZYME
    Stewart Shuman; Fiscal Year: 2006
    ..Insights gained from the proposed studies can be exploited to develop new approaches to antifungal and anti-HIV therapies designed to block capping of the pathogen's mRNAs. ..
  8. Viral and Bacterial DNA Ligases
    Stewart Shuman; Fiscal Year: 2009
    ....
  9. mRNA Capping Enzymes
    Stewart Shuman; Fiscal Year: 2009
    ..We characterized Tgs1 and Tgs2 as cap-specific guanine-N2 methyltransferases. We aim to elucidate their mechanism and structure. ..
  10. Viral RNA Modifying Enzymes
    Stewart Shuman; Fiscal Year: 2009
    ..Poxvirus cap methyltransferase is also distinguished from the human counterpart by its reliance on a unique virus-encoded regulatory subunit. ..
  11. Vaccina Virus DNA Topoisomerase
    Stewart Shuman; Fiscal Year: 2007
    ....
  12. Viral DNA and RNA Ligases
    Stewart Shuman; Fiscal Year: 2007
    ....
  13. Viral RNA Modifying Enzymes
    Stewart Shuman; Fiscal Year: 2007
    ..Poxvirus cap methyltransferase is also distinguished from the human counterpart by its reliance on a unique virus-encoded regulatory subunit. ..
  14. mRNA Capping Enzymes
    Stewart Shuman; Fiscal Year: 2007
    ..We characterized Tgs1 and Tgs2 as cap-specific guanine-N2 methyltransferases. We aim to elucidate their mechanism and structure. ..
  15. VACCINIA VIRUS DNA TOPOISOMERASE
    Stewart Shuman; Fiscal Year: 2006
    ..5) Biochemical and genetic characterization of the TopIB proteins from Mycobacterium avium, Mycobacterium smegmatis, and Pseudomonas aeurginosa. ..
  16. MRNA CAPPING ENZYME
    Stewart Shuman; Fiscal Year: 2002
    ....
  17. VACCINIA VIRUS DNA TOPOISOMERASE
    Stewart Shuman; Fiscal Year: 2002
    ..With the genetic system established, it will be possible to determine which steps in vaccinia replication are affected during synchronous infection of on- permissive cells with the deltatopo virus. ..
  18. VACCINIA VIRUS DNA TOPOISOMERASE I
    Stewart Shuman; Fiscal Year: 1993
    ..The third approach, genetically based, will be to isolate virus mutants affected conditionally in DNA topoisomerase activity so as to understand more fully the physiologic role of this enzyme in vivo...
  19. VACCINIA VIRUS MRNA TRANSCRIPTION TERMINATION
    Stewart Shuman; Fiscal Year: 1993
    ..g. c-myc) during tumorigenesis, and in the genetic program of human immunodeficiency virus (HIV), the causative agent of AIDS...