Research Topics | SUSE B BROYDESummaryAffiliation: New York University Country: USA Publications
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Publications
Lesion processing: high-fidelity versus lesion-bypass DNA polymerasesSuse Broyde
Department of Biology, New York University, 100 Washington Square East, 1009 Silver Center, New York, NY 10003, USA
Trends Biochem Sci 33:209-19. 2008....
DNA adduct structure-function relationships: comparing solution with polymerase structuresSuse Broyde
Department of Biology, New York University, New York NY 10003, USA
Chem Res Toxicol 21:45-52. 2008..While the polymerase interactions can on occasion override the solution preferences, intrinsic adduct conformations favored in solution are often manifested within polymerases and likely play a significant role in lesion processing...- Differential nucleotide excision repair susceptibility of bulky DNA adducts in different sequence contexts: hierarchies of recognition signalsYuqin Cai
Department of Chemistry, New York University, New York, NY 10003, USA
J Mol Biol 385:30-44. 2009..Furthermore, combinations of several locally destabilizing features in the hierarchy, consistent with a multipartite model, may provide a relatively strong recognition signal... 
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerasesOlga Rechkoblit
Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Structure 17:725-36. 2009..Because of homology between Dpo4 and Pol eta, such a dynamic screening mechanism might be utilized by Dpo4 and Pol eta to regulate error-free versus error-prone bypass of oxoG and other lesions...- 4-hydroxyequilenin-adenine lesions in DNA duplexes: stereochemistry, damage site, and structureShuang Ding
Department of Chemistry and Department of Biology, New York University, 100 Washington Square East, New York, New York 10003
Biochemistry 46:182-91. 2007..These characteristics may manifest themselves in terms of differential nucleotide excision repair susceptibilities and mutagenic activities of the 4-OHEN-A and C adducts... - Conformational searches elucidate effects of stereochemistry on structures of deoxyadenosine covalently bound to tumorigenic metabolites of benzo[C] phenanthreneMin Wu
Department of Chemistry, New York University, New York, NY 10003, USA
Front Biosci 9:2807-18. 2004.... - Extending the understanding of mutagenicity: structural insights into primer-extension past a benzo[a]pyrene diol epoxide-DNA adductRebecca A Perlow
Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA
J Mol Biol 327:797-818. 2003..These studies reveal in molecular detail the kinds of specific structural interactions that determine the function of a processive DNA polymerase when challenged by a bulky DNA adduct... - Increased flexibility enhances misincorporation: temperature effects on nucleotide incorporation opposite a bulky carcinogen-DNA adduct by a Y-family DNA polymeraseRebecca A Perlow-Poehnelt
Department of Biology, New York University, New York, New York 10003, USA
J Biol Chem 282:1397-408. 2007..The observed temperature effect suggests that conformational flexibility plays a role in nucleotide incorporation and bypass fidelity opposite (+)-ta-[BP]G by Dpo4... - Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesionOlga Rechkoblit
Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
PLoS Biol 4:e11. 2006.... - Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studiesLing Zhang
Department of Chemistry, New York University, New York, NY, USA
Nucleic Acids Res 34:3326-37. 2006..2006), PLoS Biol., 4, e11). However, N2-dG adducts, which can reside on the minor groove side, appear to cause less hindrance when in this position... - Thermodynamic and structural factors in the removal of bulky DNA adducts by the nucleotide excision repair machineryNicholas E Geacintov
Chemistry Department, New York University, New York, NY 10003 5180, USA
Biopolymers 65:202-10. 2002..These structural effects correlate with the differential NER susceptibilities and stem from the intrinsically distinct shapes of the fjord and bay region PAH diol epoxide-N(6)-adenine adducts... - Relating repair susceptibility of carcinogen-damaged DNA with structural distortion and thermodynamic stabilityMin Wu
Department of Chemistry, New York University, New York, NY 10003, USA
Nucleic Acids Res 30:3422-32. 2002..These differences are due to the different intrinsic topologies of the rigid, planar bay region adducts versus the twisted, sterically hindered fjord region adducts... - DNA adducts from a tumorigenic metabolite of benzo[a]pyrene block human RNA polymerase II elongation in a sequence- and stereochemistry-dependent mannerRebecca A Perlow
Department of Biology, New York University, 100 Washington Square East, Mail Code 5181, New York 10003, USA
J Mol Biol 321:29-47. 2002..It is likely that these differences between the behaviors of T7RNAP and human RNAPII are a result of the structural characteristics of the enzymes' active sites, a hypothesis that is explored in light of their known crystal structures... - Exploring damage recognition models in prokaryotic nucleotide excision repair with a benzo[a]pyrene-derived lesion in UvrBLei Jia
Department of Biology, New York University, 100 Washington Square East, Room 1009, New York, New York 10003, USA
Biochemistry 48:8948-57. 2009.... - Influence of local sequence context on damaged base conformation in human DNA polymerase iota: molecular dynamics studies of nucleotide incorporation opposite a benzo[a]pyrene-derived adenine lesionKerry Donny-Clark
Department of Biology, New York University, New York, NY 10003, USA
Nucleic Acids Res 37:7095-109. 2009..With syn dA*, there is also an opportunity for increased misincorporation of dGTP. These results expand our understanding of the versatility and flexibility of polymerase iota and its lesion bypass functions in humans... - Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacementNa Zhang
Program in Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
J Mol Biol 346:951-65. 2005..Such conformational differences in methylated and unmethylated CpG sequences may be significant because of potential alterations in the cellular processing of the [BP]G adducts by DNA transcription, replication, and repair enzymes... - The N-clasp of human DNA polymerase kappa promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesionsLei Jia
Department of Biology and Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA
Nucleic Acids Res 36:6571-84. 2008..Absence of the N-clasp in Dpo4 explains the error-prone processing of the same lesion by this enzyme. Thus, our studies elucidate structure-function relationships in the fidelity of lesion bypass... - A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structureYuqin Cai
Department of Biology, New York University, New York, New York 10003, United States
Biochemistry 49:9943-5. 2010..These findings suggest that such lesions should be as resistant to NER in the nucleosome environment as they are in free DNA... - Dynamics of a benzo[a]pyrene-derived guanine DNA lesion in TGT and CGC sequence contexts: enhanced mobility in TGT explains conformational heterogeneity, flexible bending, and greater susceptibility to nucleotide excision repairYuqin Cai
Department of Chemistry, New York University, New York, NY 10003, USA
J Mol Biol 374:292-305. 2007.... - A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) allows Watson-Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4)Lihua Wang
Biology Department, New York University, New York, NY 10003, USA
Nucleic Acids Res 34:785-95. 2006..Possible relevance of our new major groove structure for AAF-dG to other polymerases, lesion repair and solution conformations are discussed... - Role of base sequence context in conformational equilibria and nucleotide excision repair of benzo[a]pyrene diol epoxide-adenine adductsShixiang Yan
Department of Chemistry, New York University, New York, New York 10003, USA
Biochemistry 42:2339-54. 2003..Such sequence specific differential repair could contribute to the existence of mutational hotspots and thereby contribute to the complexity of cancer initiation... - Simulating structural and thermodynamic properties of carcinogen-damaged DNAShixiang Yan
Department of Chemistry, New York University, New York, NY 10003, USA
Biophys J 84:2137-48. 2003..The structural and thermodynamic features of these stereoisomeric adducts are also discussed in relation to their reported low susceptibilities to nucleotide excision repair... - Accurate representation of B-DNA double helical structure with implicit solvent and counterionsLihua Wang
Biology Department, New York University, New York, New York 10003, USA
Biophys J 83:382-406. 2002.... - The spacious active site of a Y-family DNA polymerase facilitates promiscuous nucleotide incorporation opposite a bulky carcinogen-DNA adduct: elucidating the structure-function relationship through experimental and computational approachesRebecca A Perlow-Poehnelt
Department of Biology, New York University, New York, NY 10003, USA
J Biol Chem 279:36951-61. 2004.... - Deformations of promoter DNA bound to carcinogens help interpret effects on TATA-element structure and activityQing Zhang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, 251 Mercer Street, New York, NY 10012, USA
Philos Transact A Math Phys Eng Sci 362:1479-96. 2004..The unravelled structures and interactions thus reveal the effect of different adduct locations on TATA-TBP complex formation and suggest how transcription initiation may be affected by the presence of a bulky BP... - Polymerase beta simulations suggest that Arg258 rotation is a slow step rather than large subdomain motions per seLinjing Yang
Department of Chemistry and Courant, Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, 251 Mercer Street, New York, New York 10012, USA
J Mol Biol 317:651-71. 2002..These results suggest new lines of experimentation in the study of polymerase mechanisms (e.g. enzyme mutants), which should provide further insights into mechanisms of error discrimination and DNA synthesis fidelity... - Following an environmental carcinogen N2-dG adduct through replication: elucidating blockage and bypass in a high-fidelity DNA polymerasePingna Xu
Department of Biology, New York University, New York, NY, USA
Nucleic Acids Res 35:4275-88. 2007..In vivo, a switch to a potentially error-prone bypass polymerase likely dominates translesion bypass... - The sequence dependence of human nucleotide excision repair efficiencies of benzo[a]pyrene-derived DNA lesions: insights into the structural factors that favor dual incisionsKonstantin Kropachev
Department of Chemistry, New York University, New York, NY 10003, USA
J Mol Biol 386:1193-203. 2009..These results demonstrate that the identical lesion can be repaired with markedly variable efficiency in different local sequence contexts that differentially alter the structural features of the DNA duplex around the lesion site... - Spiroiminodihydantoin lesions derived from guanine oxidation: structures, energetics, and functional implicationsLei Jia
Department of Chemistry, New York University, New York, New York 10003, USA
Biochemistry 44:6043-51. 2005..In addition, stereoisomer-specific differences indicate the possibility that their processing by cellular replication and repair enzymes may be differentially affected by their absolute configuration... - Visualizing sequence-governed nucleotide selectivities and mutagenic consequences through a replicative cycle: processing of a bulky carcinogen N2-dG lesion in a Y-family DNA polymerasePingna Xu
Department of Biology, New York University, 1009 Silver Center, 100 Washington Square East, New York, New York 10003, USA
Biochemistry 48:4677-90. 2009.... - Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot contextFabián A Rodríguez
Department of Chemistry, New York University, New York, NY, USA
Nucleic Acids Res 35:1555-68. 2007..The minor groove width opens near the lesion in both cases, but more for 5'- ... CGG*C.... Differential sequence-dependent removal rates of this lesion result and may contribute to the mutation hotspot phenomenon... - Accommodation of an N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adduct in the active site of human DNA polymerase iota: Hoogsteen or Watson-Crick base pairing?Kerry Donny-Clark
Department of Biology and Chemistry, New York University, New York, New York 10003, USA
Biochemistry 48:7-18. 2009..This suggests the possibility of an expanded role for poliota in lesion bypass... - NMR and computational studies of stereoisomeric equine estrogen-derived DNA cytidine adducts in oligonucleotide duplexes: opposite orientations of diastereomeric formsNa Zhang
Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Biochemistry 48:7098-109. 2009..These differences in stereoisomeric adduct conformations may play a role in the processing of these lesions in cellular environments... - Absolute configurations of DNA lesions determined by comparisons of experimental ECD and ORD spectra with DFT calculationsShuang Ding
Department of Biology, New York University, New York, USA
Chirality 21:E231-41. 2009..Establishing the stereochemistry of DNA lesions is highly useful for understanding their biological impact, especially when sufficient amounts of material are not available for other methods of structural characterization... - Equilenin-derived DNA adducts to cytosine in DNA duplexes: structures and thermodynamicsShuang Ding
Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, USA
Biochemistry 44:14565-76. 2005..The unusual structures and the stereochemical effects underlie their biological processing as miscoding DNA lesions whose mutagenic properties may contribute to breast cancer... - Structural and thermodynamic features of spiroiminodihydantoin damaged DNA duplexesLei Jia
Department of Chemistry, New York University, New York, New York 10003, USA
Biochemistry 44:13342-53. 2005..The structural characteristics may relate to observed mutagenic properties of the Sp stereoisomers, including possible stereoisomer-dependent differences... - Molecular dynamics of a food carcinogen-DNA adduct in a replicative DNA polymerase suggest hindered nucleotide incorporation and extensionLing Zhang
Department of Chemistry, New York University, New York, New York 10003, USA
Chem Res Toxicol 18:1347-63. 2005..Polymerase stalling would be the more common outcome and in vivo could lead to switch to an error-prone bypass polymerase... - Distant neighbor base sequence context effects in human nucleotide excision repair of a benzo[a]pyrene-derived DNA lesionYuqin Cai
Department of Biology, New York University, New York, NY 10003, USA
J Mol Biol 399:397-409. 2010.... - Toward understanding the mutagenicity of an environmental carcinogen: structural insights into nucleotide incorporation preferencesRebecca A Perlow
Department of Biology, New York University, New York, NY 10003, USA
J Mol Biol 322:291-309. 2002..Structural rationalization of the incorporation preference opposite (+)-trans-anti-[BP]-N(2)-dG by T7 DNA polymerase contributes to providing a molecular explanation for mutations caused by this carcinogen-DNA adduct in a model system... - Polymerase-tailored variations in the water-mediated and substrate-assisted mechanism for nucleotidyl transfer: insights from a study of T7 DNA polymeraseLihua Wang
Biology Department, New York University, New York, NY 10003, USA
J Mol Biol 389:787-96. 2009..These unifying features are likely requisite elements for nucleotidyl transfer reactions... - Local deformations revealed by dynamics simulations of DNA polymerase Beta with DNA mismatches at the primer terminusLinjing Yang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, 251 Mercer Street, 10012, New York, NY, USA
J Mol Biol 321:459-78. 2002.... - Substrate discrimination by formamidopyrimidine-DNA glycosylase: distinguishing interactions within the active siteRebecca A Perlow-Poehnelt
Department of Biology, New York University, 100 Washington Square East, Room 1009M, New York, New York 10003, USA
Biochemistry 43:16092-105. 2004.... - Transcription elongation past O6-methylguanine by human RNA polymerase II and bacteriophage T7 RNA polymeraseAlexandra Dimitri
Department of Biology, New York University, 1009 Silver Center, 100 Washington Square East, New York, NY 10003, USA
Nucleic Acids Res 36:6459-71. 2008..In addition, the partial blockage of RNA polymerase II suggests that transcription-coupled DNA repair could play an auxiliary role in the clearance of this lesion... - A water-mediated and substrate-assisted catalytic mechanism for Sulfolobus solfataricus DNA polymerase IVLihua Wang
Biology and Chemistry Departments, New York University, New York, NY 10003, USA
J Am Chem Soc 129:4731-7. 2007..This WMSA mechanism takes specific advantage of the unique structural features of this low-fidelity lesion-bypass Y-family polymerase, which has a more spacious and solvent-exposed active site than replicative and repair polymerases... - Lesion specificity in the base excision repair enzyme hNeil1: modeling and dynamics studiesLei Jia
Department of Chemistry, New York University, 100 Washington Square East, Room 1001, New York, New York 10003, USA
Biochemistry 46:5305-14. 2007.... - Transcription processing at 1,N2-ethenoguanine by human RNA polymerase II and bacteriophage T7 RNA polymeraseAlexandra Dimitri
Department of Biology, New York University, New York, NY 10003, USA
J Mol Biol 375:353-66. 2008..Thus, our data suggest that this repair pathway is likely engaged in the clearance of the 1,N(2)-epsilon G from actively transcribed DNA... - Conformations of stereoisomeric base adducts to 4-hydroxyequileninShuang Ding
Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, USA
Chem Res Toxicol 16:695-707. 2003..Such opposite orientations could cause stereoisomer pairs of lesions to respond differently to DNA replication and repair enzymes... - Nucleotide selectivity opposite a benzo[a]pyrene-derived N2-dG adduct in a Y-family DNA polymerase: a 5'-slippage mechanismPingna Xu
Department of Biology, New York University, 1009 Silver Center, 100 Washington Square East, New York City, New York 10003, USA
Biochemistry 47:2701-9. 2008..In addition, the dATP can be misincorporated opposite the adduct. The 5'-slippage pattern may be generally facilitated in cases where the base 3' to the lesion is the same as the adducted base... - Accommodation of a 1S-(-)-benzo[c]phenanthrenyl-N6-dA adduct in the Y-family Dpo4 DNA polymerase active site: structural insights through molecular dynamics simulationsLihua Wang
Department of Biololgy, New York University, New York, New York 10003, USA
Chem Res Toxicol 18:441-56. 2005..Furthermore, these models suggest how error-prone translesion synthesis by Y-family polymerases might produce mutations that may play a role in the initiation of cancer... - Flexible 5-guanidino-4-nitroimidazole DNA lesions: structures and thermodynamicsLei Jia
Department of Chemistry, New York University, New York, New York 10003, USA
Biochemistry 45:6644-55. 2006..However, hydrogen bonding interactions between NI and partner G or A are also found, which would be compatible with the observed mismatches... - Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine lesion by Y-family polymerase Dpo4Olga Rechkoblit
Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Nat Struct Mol Biol 17:379-88. 2010..Further extension leads to semitargeted mutations via this proposed polymerase-guided mechanism... - Altering DNA polymerase incorporation fidelity by distorting the dNTP binding pocket with a bulky carcinogen-damaged templateS Frank Yan
Department of Chemistry, New York University, New York, New York 10003, USA
Biochemistry 43:7750-65. 2004..Furthermore, plausible structural explanations for the observed effects of [BP]-N(6)-dA adduct stereochemistry on the observed stalling patterns are proposed... - Conformational analysis of a 4-hydroxyequilenin Guanine adduct using density functional theoryShixiang Yan
Department of Chemistry, New York University, 1001 Main Building, 31 Washington Place, New York 10003, USA
Chem Res Toxicol 15:648-53. 2002..Since the Watson-Crick hydrogen bonding edge of the modified guanine is obstructed by the formation of this bulky nonplanar adduct, it likely would reside in a groove of the DNA double helix... - Highly organized but pliant active site of DNA polymerase beta: compensatory mechanisms in mutant enzymes revealed by dynamics simulations and energy analysesLinjing Yang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, New York, New York, USA
Biophys J 86:3392-408. 2004.... - Structural and stereoisomer effects of model estrogen quinone-derived DNA adducts: N6-(2-hydroxyestron-6(alpha,beta)-yl)-2'-deoxyadenosine and N2-(2-hydroxyestron-6(alpha,beta)-yl)-2'-deoxyguanosineLihua Wang
Biology Department and Chemistry Department, New York University, New York, New York 10003, USA
Chem Res Toxicol 17:311-24. 2004..Stereochemistry-dependent differences in adduct orientation could be expected to produce different biochemical effects, as has been observed in adducts derived from polycyclic aromatic hydrocarbons... - Human RNA polymerase II is partially blocked by DNA adducts derived from tumorigenic benzo[c]phenanthrene diol epoxides: relating biological consequences to conformational preferencesThomas M Schinecker
Department of Biology, New York University, 100 Washington Square East, MC 5181, New York, NY 10003, USA
Nucleic Acids Res 31:6004-15. 2003.... - Conformational properties of equilenin-DNA adducts: stereoisomer and base effectsShuang Ding
Departments of Biology and Chemistry, New York University, 100 Washington Square East, New York City, New York 10003, USA
Chem Res Toxicol 21:1064-73. 2008..These differences may underlie observed differential stereoisomer and base-dependent mutagenicities and repair susceptibilities of these adducts... - Determination of absolute configurations of 4-hydroxyequilenin-cytosine and -adenine adducts by optical rotatory dispersion, electronic circular dichroism, density functional theory calculations, and mass spectrometryShuang Ding
Department of Biology, New York University, New York, 10003, USA
Chem Res Toxicol 21:1739-48. 2008..The absolute configurations of the 4-OHEN-dA adducts were thus deduced by comparing the experimental ORD with computed ORD values of 4-OHEN-A adducts... - Transcription of DNA containing the 5-guanidino-4-nitroimidazole lesion by human RNA polymerase II and bacteriophage T7 RNA polymeraseAlexandra Dimitri
Department of Biology, New York University, New York, NY 10003 6688, USA
DNA Repair (Amst) 7:1276-88. 2008..These influence the kinetics of lesion bypass and may well play a role in TM and TCR in cells...
Research Grants
- Carcinogen-DNA Adducts: Topology, Conformation and Repair (Renewal)Suse Broyde; Fiscal Year: 2010..In addition, design of more efficacious cancer chemotherapeutic agents will be facilitated. ..
- AF AND AAF MODIFIED DNA STRUCTURES--MUTAGENIC RELEVANCESuse Broyde; Fiscal Year: 2000....
- Aromatic Amine DNA Structures--Mutagenic RelevanceSuse Broyde; Fiscal Year: 2005..Molecular dynamics trajectories yield ensembles of structures that will be used to compute free energy differences between conformers in solution, and binding free energies of polymerase-primer-template complexes. ..
- DNA Lesion Structures: Mutagenicity and RepairSuse Broyde; Fiscal Year: 2010....
- DNA Lesion Structures: Mutagenicity and RepairSuse Broyde; Fiscal Year: 2009....
- Carcinogen - DNA Adducts: Linkage Site and ConformationSuse Broyde; Fiscal Year: 2009..The long term goals are to define conformational details governing NER and translesion DNA synthesis to gain predictive power relating lesion structure with carcinogenic hazard. ..
- DNA Lesion Structures: Mutagenicity and RepairSuse Broyde; Fiscal Year: 2007....
- Carcinogen - DNA Adducts: Linkage Site and ConformationSuse Broyde; Fiscal Year: 2007..The long term goals are to define conformational details governing NER and translesion DNA synthesis to gain predictive power relating lesion structure with carcinogenic hazard. ..
- CARCINOGEN/DNA ADDUCTS--LINKAGE SITE AND CONFORMATIONSuse Broyde; Fiscal Year: 1999....
- CARCINOGEN-DNA ADDUCTS LINKAGE SITE AND CONFORMATIONSuse Broyde; Fiscal Year: 1993..In addition, it is planned to automate and document DUPLEX, and release it to the scientific community...