Assistant Professor, Department of Microbiology and Molecular Genetics
Education & Training
- Postdoctoral Fellow
- Duke University; University of Pittsburgh
- University of Chicago, 2000
Dr. Kim received her B.S. in Chemistry at the University of Chicago. She then did her Ph. D. thesis research with Ursula Storb in the department of Biochemistry and Molecular Biology at the University of Chicago studying the mechanism of somatic hypermutations in the mouse and human immunoglobulin genes. Her first postdoctoral research involved characterization of a novel DNA polymerase carried out in the laboratory of Richard Wood at the University of Pittsburgh. She then joined the lab of Sue Jinks-Robertson at Emory University for her second postdoctoral training and begun research into how transcription directly influences genome instability using the Saccharomyces cerevisiae model system. She moved to Duke University with the rest of the Jinks-Robertson lab and was later promoted to research assistant professor. She joined the MMG department at UT Health Science Center at Houston in 2013 as an assistant professor.
Mechanisms of mutagenesis and chromosomes rearrangements in
Alterations to the genome, from simple mutations to chromosome rearrangements, are prerequisite to evolution as well as a pervasive feature of various somatic diseases. In many cancers, the disturbance of normal cellular activities associated with oncogenic transformation initiates with changes in the genome. Identifying key factors affecting genome stability is, therefore, central to understanding how cancer develops.
Transcription, although it is generally considered distinctly separate, shares the genomic DNA as template with replication and repair processes. The observation that certain highly transcribed genes are hotspots of spontaneous recombination and mutagenesis demonstrates the importance of the interplay among transcription, replication, and repair in genome maintenance. Our research objective is to better understand the molecular basis of transcription-associated recombination (TAR) and mutagenesis (TAM) through genetic approaches in the model organism, Saccharomyces cerevisiae.
In highly transcribed areas of the yeast genome, a higher rate of mutagenesis as well as a unique spectrum of mutations have been observed. Recent discoveries point to the accumulation of endogenous DNA damages as the main cause of such transcription-associated genome instability. In particular, an elevated incorporation of atypical nucleotides such as uracil and ribonucleotides in highly transcribed regions of the yeast genome results in accumulation of unique types of mutations such as A:T to C:G base changes and short deletions at tandem repeats. 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 research interest in the lab involves the formation of non-canonical/non-B form DNA structures during activated transcription. Such structures can hinder the efficient movement of DNA replication and potentially lead to elevated genomic instability. An example of such “At-Risk-Motifs” (ARMS) is the highly G/C rich and repetitive sequence that assemble into a G-quadruplex or G4 DNA structure with runs of guanines forming stable G quartets. By integrating G4 DNA-forming sequence motifs into the yeast genome, we are studying how such sequences become hotspots of genome instability and contribute to gross chromosomal rearrangements.
Owiti, N., Lopez, C., Singh, S., Stephenson, A., and Kim, N. 2017. “Def1 and Dst1 play distinct roles in repair of AP lesions in highly transcribed genomic regions.” DNA Repair 55: 31 – 39.
Lopez, C.R., Singh, S., Hambarde, S., Griffin, W.C., Gao, J., Chib, S., Yu, Y., Ira, G., Raney, K.D., and Kim, N. “Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.” Nucleic Acids Research 45(10): 5850 – 5862.
Yadav, P., Owiti, N., and Kim, N. 2015 “The role of topoisomerase I in suppressing genome instability associated with a highly transcribed guanine-rich sequence is not restricted to preventing RNA:DNA hybrid accumulation.” Nucleic Acids Research. Epublished.
Yadav, P., Harcy, V., Argueso, J-L., Dominska, M., Jinks-Robertson, S., and Kim, N. 2014 “Topoisomerase I plays a critical role in suppressing genome instability at a highly transcribed G-quadruplex-forming sequence” PLoS Genetics 10(12): e1004839.
Kim, N., Cho, J-E., Li, Y. C., and Jinks-Robertson, S. 2013 “RNA:DNA Hybrids Initiate Quasi-Palindrome-Associated Mutations in Highly Transcribed Yeast DNA” Plos Genetics 9(11):e1003924.