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Linlin Zhao

​​​Assistant Professor
Chemistry
Biosciences 4112
989-774-3252
Education
  • Postdoctoral, Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 2010-2013
  • Ph.D., Bioanalytical Chemistry, University of Connecticut, Storrs, CT, 2010 
  • B.S., Chemistry, Jilin University, Changchun, Jilin, China, 2005
Affiliations
American Chemical Society (ACS); American Society of Biochemistry and Molecular Biology (ASBMB); American Society of Mass Spectrometry (ASMS)
Research Interests
​The integrity of human genome is critical for human health.  However, our genetic material, DNA, is under the threat of thousands of endogenous and exogenous chemicals.  Many of these chemicals can react with DNA either directly or after metabolic activations, resulting in various DNA adducts or DNA lesions.  Although many DNA lesions can be repaired by DNA repair proteins, certain lesions are poorly repaired and can encounter DNA polymerases (key enzymes responsible for copying DNA) during DNA replication.  These "abnormal" DNA structures can disrupt the regular functions of DNA polymerases and cause replication stalling, mutations, or cell death, etc.

Organisms from bacteria to humans are equipped with special DNA polymerases to bypass various DNA lesions to ensure continuous DNA replication.  These special DNA polymerases are known as translesion synthesis (TLS) DNA polymerases.  The TLS process, however, comes at a price of introducing​ errors into genome.  Thus TLS is particularly important to human health and disease.

Dr. Zhao's research team is interested in the biochemical properties and functions of human TLS DNA polymerases.  Our current projects focus on investigating how DNA lesions perturb TLS DNA polymerases.  We use highly interdisciplinary approaches that involve chemistry, biochemistry, molecular biology, and structural biology to gain mechanistic insight​ into the deleterious effects induced by DNA damage. 
Teaching Areas
Biochemistry, Analytical Chemistry, General Chemistry
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Selected Publications

  • Zhao, L* and Washington MT, Translesion synthesis: insights into the selection and switching of DNA polymerases, Genes (Basel), 20178, 24. 
  • Xu, W; Kool, D; O’Flaherty, DK; Keating AM; Sacre L; Egli, M; Noronha A; Wilds, CJ; Zhao, L*  O6-2′-deoxyguanosine-butylene-O6-2′-deoxyguanosine DNA interstrand cross-links are replication-blocking and mutagenic DNA lesions.  Chem. Res. Toxicol. 2016, 29, 1872-1882.​
  • Xu, W; Ouellette, AM; Souradyuti Ghosh, Tylor CO; Greenberg MM; Zhao, L* Mutagenic bypass of an oxidized abasic lesion-induced DNA interstrand cross-link analogue by human translesion synthesis DNA polymerases. Biochemistry, 2015, 54, 7409-7422.
  • ​Xu, W; Ouellette, AM; Wawrzak, Z; Shriver SJ. Anderson, SM; Zhao, L*. Kinetic and structural mechanisms of (5'S)-8,5'-cyclo-2'-deoxyguanosine-induced DNA replication stalling, Biochemistry, 2015, 54, 639-651.
  • Zhao, L*; Pence, M; Eoff, R; Yuan S; Fercu, C; Guengerich, FP*. Elucidation of kinetic mechanisms of human tranlesion DNA polymerase kappa using tryptophan mutants. FEBS J, 2014, 281, 4394-4410.
  • Zhao, L.; Pence, MG; Christov, PP; Wawrzak, Z; Choi, JY; Rizzo, CJ; Egli, M; Guengerich, FP. Basis of miscoding of the DNA adduct N2,3-ethenoguanine by human Y-family DNA polymerases, J. Biol. Chem., 2012, 287, 33516-33526. (featured on the cover)
  • Zhao, L.; Christov, PP; Kozekov, ID; Pence, MG; Pallon, PS; Rizzo, CJ; Egli, M; Guengerich, FP. Replication of N2,3-ethenoguanine by DNA polymerases, Angew. Chem. Int. Ed., 2012, 51, 5466-5469.
  • Zhao, L.; Schenkman, JB; Rusling, JF. High throughput genotoxicity screening using magnetic bioreactors with LC-MS/MS, Anal. Chem., 2010, 82, 10172-10178.
  • Zhao, L.; Schenkman, JB; Rusling, JF. Screening for reactive metabolites using electro-optical arrays featuring human liver cytosol and microsomal enzyme sources and DNA, Chem. Comm., 2009, 5386-5388. (highlighted as hot article)
  • Zhao, L; Krishnan, S; Zhang, Y; Schenkman, JB; Rusling, JF. Differences in metabolite-mediated toxicity of tamoxifen in rodents versus humans elucidated with DNA/microsome electro-optical arrays and nanoreactors, Chem. Res. Toxicol., 2009, 22, 341-347.​