Chromosome Stability Group
Repair, Replication, Mutation & Stress Signaling
Michael A. Resnick, Ph.D.
The Chromosomal Stability Group (CSG) integrates mechanisms and genetic controls of genome stability with environmental factors and stress signaling to better understand their complex contributions to human health. Using budding yeast and human cell models, CSG focuses on genome maintenance and natural or environmental challenges to chromosome stability. Because of similarities in genome organization, enzymatic processes and genetic controls, findings with yeast are often applicable to human disease.
Repair, recombination, mutagenesis and checkpoint functions are investigated to understand sources of genome instability and mechanisms of coping with DNA damage, particularly double-strand breaks (DSBs). The functionality of human genes and networks are examined in these processes, with special emphasis on the prominent p53 tumor suppressor and stress responses. To facilitate these studies, the CSG develops a variety of highly sensitive systems for identifying subtle genome variations and responses that extend from chromosomal at-risk motifs (ARMs) and structures to regulated transactivation by human master regulators.
Major areas of research:
- Genetic and structure-function relationships in replication, repair and mutation avoidance (also see Dmitry Gordenin: Chromosome Stability Group)
- Sources of double-strand breaks, genetic consequences and mechanisms of repair
- Organization and evolution of p53 tumor suppressor master regulatory network and consequences of mutations
- Environmental agents and conditions that impact genome stability
- Mechanisms of DSB repair and coordination of end-processing to generate single-strand DNA
- Hypermutability of single-strand DNA in yeast
- Translating yeast findings on mutagenesis and hypermutability to human cancers and the impact of DNA deaminating protein(s) APOBEC3
- Characterizing the expanding universe of p53 targets
- Determining p53 role in human immune/inflammatory systems, including the innate immune TLR (toll-like receptor) genes, within human primary and cancer cells.
- Human variability in p53-associated stress responses
Overall, our studies have resulted in novel mechanistic approaches to clinically relevant diseases that may have strong environmental components. These combined yeast and human cell approaches increase our understanding of environmental factors that put human genome stability and health at risk and provide opportunities for interventions.Michael A. Resnick, Ph.D., head of the Chromosome Stability Group, received his Ph.D. from the U. California, Berkeley, and did postdoctoral work with the Medical Research Council in London and Oak Ridge National Laboratories. He held faculty positions at the U. Rochester, NY, the National Institute for Medical Research, London, and has been with NIEHS since 1979. He has authored approximately 170 peer-reviewed articles, 50 reviews and book chapters, and holds 7 patents. His group has received a “Best Paper of the Year” at NIEHS five times since its inception in 2003. He received the 2008 NIEHS Scientist of Year Award and was elected Fellow of the American Association for the Advancement of Science (AAAS) in 2012.