MOLECULAR MECHANISMS OF RNA-MEDIATED DNA REPAIR AND MODIFICATION

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.Ph.D