Doctor of Philosophy in Biology

in the 

School of Biological Sciences

Chance Meers

will defend his dissertation

Molecular Mechanisms of RNA-mediated DNA Repair and Modification 

Wednesday, January 8th, 2019

3:00 PM

Krone Engineered Biosystems Building

Children's Healthcare of Atlanta Seminar Room (1005)

Thesis Advisor:

Dr. Francesca Storici

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Kirill Lobachev

School of Biological Sciences

Georgia Institute of Technology

Dr. Frank Rosenzweig

School of Biological Sciences

Georgia Institute of Technology

Dr. Loren Williams

School of Chemistry and Biochemistry

Georgia Institute of Technology

Dr. Anita Corbett

Department of Biology

Emory University 

Abstract

Genomic stability is essential in maintaining the accurate inheritance of genetic material from mother to daughter cell. However, endogenous and exogenous stresses are continuously attacking and damaging genetic information. In responses, cells developed mechanisms to prevent and correct these damages. DNA can be damaged in a variety of different ways, with DNA double-stranded breaks being one of the most dangerous lesions. We recently showed that RNA can be used as a template for repair in budding yeast. Here, we investigate the molecular mechanisms by which RNA can template the repair of DNA damage. We determine the role of endogenous retrotransposons and characterize molecular components that are required for repair by reverse transcribed transcript-RNA. To better understand the role of RNA in directly templating DNA repair, we eliminated components required for retrotransposon-mediated repair events to find that RNA can directly template double-strand break repair. We show that this process is strongly reliant on translesion DNA polymerase ζ (Zeta). Remarkably, we uncover a role of RNA directly modifying genomic DNA in the absence of induced DNA damage, revealing a novel role of translesion DNA synthesis.