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Cynthia J. Burrows

Distinguished Professor and Chair of Chemistry

Cynthia Burrows

B.A. University of Colorado, Boulder

Ph.D. Cornell University

Research

References

burrows@chem.utah.edu

Cynthia Burrows' Lab Page

Cynthia Burrows' PubMed Literature Search

Biological Chemistry Program

Nucleic Acid Chemistry

Research

The heterocyclic bases of nucleic acids are rich targets for both toxins that damage DNA and drugs that interact with DNA and RNA.   Our laboratory investigates several different aspects of nucleic acid chemistry with particular emphasis on oxidative damage to DNA bases.   Tools used in our lab include synthesis of modified nucleic acids, organic reaction mechanisms, structural analysis by ESI-MS and NMR, gel electrophoresis, PCR and enzyme biochemistry related to DNA polymerases.

Chemistry and Biochemistry of Guanine Oxidation   Many health problems ranging from cancer to aging stem from oxidative damage to DNA.   Within DNA, guanine is the site most susceptible to oxidation.   We are currently investigating the mechanistic pathways of one-electron oxidation of G to 8-oxoG and leading on to guanidinohydantoin and spirodihydantoin products.   Both the misinsertion of bases opposite new lesions by polymerases and their repair by DNA repair enzymes (the latter in collaboration with Sheila David) are under investigation.   In RNA, oxidation of Gs forms the basis of a structural probe of this residue.

Burrows Figure Two

DNA-Protein Cross-Links.   DNA oxidation can also lead to the formation of covalent adducts to bases, and the lysine-rich motifs that bind DNA provide abundant nucleophiles for cross-linking.   Studies current include the elucidation of the structures and mechanisms by which oxidation of either DNA or a protein can lead to cross-link formation as well as investigations of other cellular nucleophiles such as spermine.   Adducts to DNA formed from oxidation of redox active phenols (tyrosine, catechols, estrogen, etc.) are also under investigation.

Burrows Figure One

References

  1. Zhang Y, Dood J, Beckstead AA, Li XB, Nguyen KV, Burrows CJ, Improta R, Kohler B (2014) Efficient UV-induced charge separation and recombination in an 8-oxoguanine-containing dinucleotide. Proc. Natl. Acad. Sci. USA 111:11612-11617
  2. Chen X, Fleming AM, Muller JG, Burrows CJ (2013) Endonuclease and Exonuclease Activities on Oligodeoxynucleotides Containing Spiroiminodihydantoin Depend on the Sequence Context and the Lesion Stereochemistry. New J. Chem. 37:3440-3449
  3. Jin Q, Fleming AM, Johnson RP, Ding Y, Burrows CJ, White HS (2013) Base-excision repair activity of uracil-DNA glycosylase monitored using the latch zone of α-hemolysin. J. Am. Chem. Soc. 135:19347-53
  4. Fleming AM, Orendt AM, He Y, Zhu J, Dukor RK, Burrows CJ (2013) Reconciliation of chemical, enzymatic, spectroscopic and computational data to assign the absolute  configuration of the DNA base lesion spiroiminodihydantoin. J. Am. Chem. Soc. 135:18191-204
  5. An N, Fleming AM, Burrows CJ (2013) Interactions of the human telomere sequence with the nanocavity of the α-hemolysin ion channel reveal structure-dependent electrical signatures for hybrid folds. J. Am. Chem. Soc. 135:8562-70
  6. Fleming AM, Burrows CJ (2013) G-quadruplex folds of the human telomere sequence alter the site reactivity and reaction pathway of guanine oxidation compared to duplex DNA. Chem. Res. Toxicol. 26:593-607
  7. An N, White HS, Burrows CJ (2012) Modulation of the current signatures of DNA abasic site adducts in the α-hemolysin ion channel. Chem. Commun. (Camb). 48:11410-2
  8. Nguyen KV, Burrows CJ (2012) Whence flavins? Redox-active ribonucleotides link metabolism and genome repair to the RNA world. Acc. Chem. Res. 45:2151-9
  9. Ghanty U, Fostvedt E, Valenzuela R, Beal PA, Burrows CJ (2012) Promiscuous 8-alkoxyadenosines in the guide strand of an siRNA: modulation of silencing efficacy and off-pathway protein binding. J. Am. Chem. Soc. 134:17643-52
  10. Fleming AM, Muller JG, Dlouhy AC, Burrows CJ (2012) Structural context effects in the oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine to hydantoin products: electrostatics, base stacking, and base pairing. J. Am. Chem. Soc. 134:15091-102
  11. An N, Fleming AM, White HS, Burrows CJ (2012) Crown ether-electrolyte interactions  permit nanopore detection of individual DNA abasic sites in single molecules. Proc. Natl. Acad. Sci. USA 109:11504-9
  12. Zhao X, Krishnamurthy N, Burrows CJ, David SS (2010) Mutation versus repair: NEIL1 removal of hydantoin lesions in single-stranded, bulge, bubble and duplex DNA contexts. Biochemistry 49:1658-1666
  13. Aller P, Ye Y, Wallace S, Burrows CJ, Doublié S (2010) Crystal structure of a replicative DNA polymerase bound to the oxidized guanine lesion guanidinohydantoin. Biochemistry 49:2502-2509
  14. Xu X, Fleming A, Muller JG, Burrows CJ (2008) Formation of Tricyclic [4.3.3.0] Adducts Between 8-Oxoguanosine and Tyrosine under Conditions of Oxidative DNA-Protein Cross-linking. J. Am. Chem. Soc. 130:10080-10081
  15. Krishnamurthy N, Zhao X, Burrows CJ, David S (2008) Superior removal of hydantoin lesions relative to other oxidized bases by the human DNA glycosylase hNEIL1. Biochemistry 47:7137-7146.
  16. Xu X, Muller JG, Ye Y, Burrows CJ (2008) DNA-protein cross-links between guanine and lysine depend on the mechanism of oxidation for formation of C5 vs. C8 adducts. J. Am. Chem. Soc. 130:703-709
  17. Munk BH, Burrows CJ, Schlegel HB (2008) An exploration of mechanisms for the transformation of 8-oxoguanine to guanidinohydantoin and spiroiminodihydantoin by density functional theory. J. Am. Chem. Soc. 130:5245-5256
  18. Krishnamurthy N, Muller JG, Burrows CJ, David SS (2007) Unusual structural features of hydantoin lesions translate into efficient recognition by Escherichia coli Fpg. Biochemistry 46:9355-9365
  19. Zhao X, Muller JG, Halasyam M, David SS, Burrows CJ (2007) In vitro DNA ligation of oligodeoxynucleotides containing oxidized purine lesions by bacteriophage T4 DNA ligase. Biochemistry 46:3734-3744
  20. Ye Y, Muller JG, Burrows CJ (2006) Synthesis and characterization of the oxidized dGTP lesions spiroiminodihydantoin-2'-deoxynucleoside-5'-triphosphate and guanidinohydantoin-2' -deoxynucleoside-5'-triphosphate. J. Org. Chem. 71:2181-2184
  21. Johansen MJ, Muller JG, Xu X, Burrows CJ (2005) Oxidatively induced DNA-protein cross-linking between single-stranded binding protein (SSB) and oligodeoxynucleotides containing 8-oxo-7,8-dihydro-2'-deoxyguanosine. Biochemistry 44:5660-5671
  22. Kornyushyna O, Stemmler AJ, Graybosch DM, Bergenthal I, Burrows CJ (2005) Synthesis of a metallopeptide-PNA conjugate and its oxidative cross-linking to a DNA target. Bioconj. Chem. 17:178-183
  23. Hosford ME, Muller JG, and Burrows CJ (2004) Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation. J. Am. Chem. Soc. 126:9540-9541

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Last Updated: 11/2/16