Chromosome Stability Group
Repair, Replication & Checkpoint Function
Michael A. Resnick, Ph.D.
Tel (919) 541-4480
Fax (919) 541-7593
P.O. Box 12233
Mail Drop D3-01
Research Triangle Park, North Carolina 27709
The Chromosomal Stability Group integrates mechanisms and genetic controls of genome stability with environmental factors and stress responses to better understand their complex contributions to human health.
Using budding yeast and human cell models, research focuses on genome maintenance and natural or environmental challenges to chromosome stability. Because of similarities in genome organization, enzymatic processes and genetic controls, findings are often applicable to human disease. Repair, replication and checkpoint functions are investigated to understand sources of genome instability and mechanisms of coping with DNA damage, particularly double-strand breaks. The functionality of human genes and networks are examined in these processes, with special emphasis on the p53 tumor suppressor. The group develops a variety of highly sensitive systems for identifying subtle genome variations and responses that extend from chromosomal at-risk motifs (ARMs) to regulated transactivation by human master regulators. These studies, several of which were considered as high-risk, have resulted in novel mechanistic approaches to clinically relevant diseases that may have strong environmental components. Ultimately, the combined yeast and human cell approaches will influence our understanding of environmental factors that put human genome stability and health at risk.
Major areas of research:
Genetic and structure-function relationships in replication, repair and mutation avoidance
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
Investigate general mechanisms of DNA repair and mutation avoidance that maintain genome stability and reduce the impact of environmental factors
Identify mechanisms of double-strand break appearance, repair, genetic controls and small or large genomic changes, employing unique genetic and physical assays
Characterize mechanisms of localized hypermutability
Understand the contribution of lagging strand and single-strand DNA components in genome instability
Determine the contribution of noncanonical response elements and SNPs to the human p53 master regulatory network and evaluate cancer-associated mutations
Michael A. Resnick, Ph.D., head of the Chromosome Stability Group within the Laboratory of Molecular Genetics, received his B.A. from Northwestern University in 1964 and his Ph.D. from the University of California, Berkeley, in 1968. He completed postdoctoral fellowships with the Medical Research Council in London and Oak Ridge National Laboratories. He then went on to faculty positions at the University of Rochester, New York, the National Institute for Medical Research, Mill Hill, London, and has been with NIEHS since 1979. He has authored approximately 140 peer-reviewed articles, many in leading biomedical journals, over 40 reviews and book chapters and co-edited several multi-contribution publications. He has received seven patents on work developed in his laboratory. Since the inception of the "Best Paper of the Year" at NIEHS in 2003, his group has received this award for 2003, 2004 and 2007. He received the 2008 NIEHS Scientist of the Year Award.