Toxicology Dissertation: Novel Mechanism Leading to Mismatch Repair Deficiency and Mutator Phenotype.
Advisor: Dr. Liya Gu
Courses taken Included:
Biomolecules and Metabolism, Biomolecules and Molecular Biology, Biochemistry, Environmental Toxicology, Integrated Biomedical Sciences, Cell signaling, Basic Statistic Analysis, Ethics in Scientific Research, Molecular Mechanisms in Toxicology, Cell Biology, Experimental Genetics, and Principles of Drug Action
Courses Taken Included:
Chemistry, General Biology I and II, General Chemistry I and II, Organic Chemistry I and II, Calculus I and II, Physics I and II, Chemical Analysis I, Biochemistry, Methods of Organic Chemistry, Physical Chemistry I and II, Inorganic Chemistry, Instrument Chemistry Analysis, and Immunology
Novel Mechanism Leading to Mismatch Repair Deficiency and Mutator Phenotype
We demonstrate that phosphorylation of proliferating cell nuclear antigen (PCNA), a MMR component required for the initiation and resynthesis steps of the repair reactions, blocks in vitro MMR and induces a mutational frequency several fold higher than non-phosphorylated PCNA. This study provided a novel mechanism by which posttranslational modifications inhibit MMR, leading to genome instability and tumorigenesis.
Ortega J, Li J, Lee S, Tong D, Gu L, Li GM. Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis, PNAS (2015) 5;112(18):5667-72
Liu S, Lv G, Zheng L, Dai H, Liu W, Li H , Xu H, Hua Y, Zhou Y, Ortega J, Li GM, Kunkel TA, and Shen B. Alpha-segment error editing by the mammalian FEN1/MutS* functional complex, EMBO J. 2015, Apr 28. pii: e201489865
Tong D, Ortega J, Kim C, Huang J, Gu L, Li GM. Arsenic Inhibits DNA Mismatch Repair by Promoting EGFR Expression and PCNA Phosphorylation, JBC. 2015, Apr 23. pii: jbc.M115.641399
Pan F, Wingo TS, Zhao Z, Street C, Yu M, Qu G, Li L, Faiola F, Nguyen L, Wang J, Makishima H, Chen S, Weeks O, Liu S, Wang J, He C, Ortega J, Li GM, Aifantis I, Yang FC, Jin P, Xu M. TET2 protects genomic stability through interaction with MSH6, Nature Genetics. 2015. (Revision, 2014-06-07693)
Mao G, Lee S, Ortega J, Gu L, Li GM. Modulation of microRNA processing by mismatch repair protein MutL*, Cell Res. 2012 Jun;22(6):973-85.
Ortega J, Orellano A., Alegría AE, González FA, Cytotoxicity of New Quinones and Polyethylenimine, Undergraduate Symposium, University of Puerto Rico, Mayagüez, Platform Presentation
Ortega J, Puppala D, Gairola CG, Swanson HI, Red Raspberry Extract on AhR & NF-B Pathways, Toxicology Summer Research Symposium, University of Kentucky, Lexington, Platform Presentation
Ortega J, Lee EY, Napier D, Ensor M, Li GM, Gu L, PCNA phosphorylation at tyrosine211 inhibits mismatch repair at the initiation step, 2010 ASBMB Experimental Biology, Anaheim, CA, Poster Presentation
Ortega J, Lee EY, Napier D, Ensor M, Li GM, Gu L, PCNA phosphorylation at tyrosine211 inhibits mismatch repair at the initiation step, Markey Cancer Research Day, Lexington, KY, Poster Presentation
Ortega J, Li J, Ensor M, Li GM, Gu L, PCNA Phosphorylation Inhibits Mismatch Repair and Induces Misincorporations during DNA Synthesis, 2011 DNA Repair Midwest Conference, Toledo, OH, Platform Presentation
Ortega J, Li J, Lee S, Gu L, Li GM, PCNA tyrosine phosphorylation by EGFR promotes genome instability, 2013 ASBMB Experimental Biology, Boston, MA, Poster Presentation
Ortega J, Li J, Lee S, Gu L, Li GM, PCNA tyrosine phosphorylation by EGFR promotes genome instability, 2013 ASBMB Experimental Biology, Ventura, CA, Poster Presentation
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