Kj Myung, Ph.D.
Genetics and Molecular Biology Branch
Genome Instability Section
B.S. Seoul National University, 1991
M.S. Seoul National University, 1993
Ph.D. Brown University, 1999
49 Convent Dr, MSC 4442
Bethesda, MD 20892-4442
Dr. Myung's laboratory investigates genome instability by examining the mechanisms of DNA repair and replication, as well as their roles in the production and suppression of gross chromosomal rearrangements (GCRs). Specifically, his group is studying how previously identified mutator genes regulate the process of genome instability, with an emphasis on exploring the instability suppression mechanism of the proteins they encode. The major goals of his group are to develop new model systems to aid in this research and to use information from his studies to develop potential chemotherapeutic agents.
Genome instability is observed in many genetic disorders and cancer. Different types have been identified, including the accumulation of mutations, chromosomal rearrangements, and aneuploidy (an abnormal number of chromosomes). These defects have been linked to faulty DNA repair and responses to DNA damage. Many are seen in tumors harboring mutations in DNA-repair genes, suggesting that genome instability defects are probably involved in tumor development.
Using a whole-genome screening method in yeast developed by his group, Dr. Myung's laboratory is studying the pathways that maintain genome stability in mammals, as well as in yeast. Currently, his group is focusing on the mechanism of action for three of these genes: ELG1, RAD5, and MPH1.
Dr. Myung's group found that GCRs are suppressed by a template-switching mechanism that involves a post-replication repair pathway principally regulated by Rad5-dependent proliferating cell nuclear antigen (PCNA) polyubiquitination. His group also recently identified mammalian RAD5 genes, called SHPRH and HLTF; the scientific community has been searching for these genes for the last 20 years. Both SHPRH and HLTF redundantly promote PCNA polyubiquitination and suppress GCR formation. Mutation or silencing of these genes has been observed in several cancers.
Dr. Myung's laboratory found that the yeast Elg1 (Enhanced level of genome instability 1) protein is involved in DNA repair, and that mutations in elg1 enhance spontaneous DNA damage, which then increases the rate of GCRs. Dr. Myung's group also identified the mammalian ELG1 that shares similar functions with yeast Elg1. Interestingly, they found that the mammalian ELG1 generates DNA damage-induced nuclear foci in response to stresses of DNA replication. Using gene-knockout and RNAi-based methods, they found that mammalian ELG1 has a unique function in regulating the level of ubiquitinated PCNA and thereby suppressing tumorigenesis.
Dr. Myung's laboratory is conducting early-stage screenings to identify small molecules that potentiate DNA replication stresses and inhibitors of ELG1-dependent DNA repair pathways. These small molecules could be potential chemotherapeutic agents.
Over the past several years, Dr. Myung and his colleagues have identified many genes that enhance GCRs when overexpressed. One of the more dramatic examples of this overexpression is MPH1, which is highly homologous to a Class M gene implicated in Fanconi anemia, and enhances GCRs by partially inactivating Rad52-dependent homologous recombination. Using yeast as a model organism, his group is currently exploring a DNA repair mechanism to repair DNA adducts produced by cross-linking agents. This particular mechanism is defective in patients with Fanconi anemia.
Last Updated: September 20, 2011