Nayun Kim, assistant professor in the department of microbiology and molecular genetics at The University of Texas Medical School, will present “Transcription and Genome Instability” as part of the School of Biological Sciences Seminar Series.
When: 4 p.m. Thursday, November 13
Where: 210 Moulton Hall
Abstract of her presentation
Cancer is a genetic disease that results from changes in the genetic material, DNA. These changes, ranging from small mutations and chromosome translocations to changes in the number of chromosomes (aneuploidy), typically precede and often instigate the unchecked growth and abnormal behavior that define cancer cells. Such genome instability events are central to understanding the changes in cells at the onset of cancer development and highly relevant to cancer treatment since many of the chemotherapeutics currently in use function by damaging DNA and elevating genome instability. Genome instability is not randomly distributed but rather concentrated at certain genomic loci, referred to as “hotspots.” We discovered that the level of transcription is an important determinant of such “hotspots” of genome instability. The nucleotide composition of the highly transcribed genomic locus is altered to include non-canonical nucleotides like ribo-nucleotides and deoxyuridine, which leads to greatly elevated rate of mutagenesis. In addition, when certain repetitive sequences are highly transcribed, it fosters the formation of unusual DNA secondary structures that can block normal cellular transactions occurring on DNA such as transcription and replication. Co-transcriptional formation of the four-stranded G-quadruplex or G4 DNA, we found, results in various types of genome instability including gross rearrangement, large deletion, and partial duplication of chromosomes. G4 DNA sequences are particularly relevant to the biology of cancer because they are frequently found at chromosome breakpoints of translocations associated with various human cancers. I will discuss the recent data suggesting that topoisomerase I enzyme plays a critical and specific function in suppressing the genome instability associated with G4 DNA structure.