Research Track Faculty
Nayun Kim, PhD
Assistant Research Professor
My research focuses on the study of how transcription contributes to genomic instability. Replication and transcription are often considered as distinctly separate processes. However, both processes utilize the genomic DNA as a template and are intertwined physically and temporally. This interconnection is evident in the observation that certain highly transcribed genes are hotspots of spontaneous recombination and mutagenesis. We are trying to better understand the molecular basis of transcription-associated recombination (TAR) and mutagenesis (TAM) through genetic approaches in the model organism, Saccharomyces cerevisiae. Using the tetracycline-regulatable promoter pTET, we demonstrated a direct and proportional relationship between the level of transcription and the rate of mutagenesis. In addition to the quantitative differences, mutations found under high transcription conditions have a unique spectrum distinct from those found under low-transcription conditions.
The tetracycline-regulatable system has so far yielded some valuable clues regarding how activated transcription can interfere with genome maintenance. We recently discovered that, in addition to the accumulation of endogenous DNA damage, there is an elevated incorporation of atypical nucleotides such as uracil and ribonucleotides in highly transcribed regions of the yeast genome. We are currently studying how the imbalance in the nucleotide composition is achieved in highly transcribed regions and how this imbalance affects genomic stability.
Another way transcription potentially leads to elevated genomic instability is by promoting the formation of non-canonical/non-B form DNA structures that can hinder the efficient DNA replication fork movement. An example of such "At-Risk-Motifs" (ARMS) is the immunoglobulin Switch Region sequences which are highly G/C rich and very repetitive. When highly transcribed, the switch region sequences assemble into a G-loop structure with runs of guanines forming stable G quartets. By integrating the Switch Region sequence into the yeast genome, we are studying how G-loops are normally processed to avoid elevated genomic instability.