Susan M. Rosenberg, Ph.D.

Molecular & Human Genetics

Nurture remodels nature: environmentally-inducible genetic change

Dr. Rosenberg received the award for her research on mutations and genome rearrangement that alter chromosome structure. These changes to a cell’s genome are the underlying causes of many medically important problems. Examples in which the human genome is changed include cancer formation, tumor progression, and evolution of cancer resistance to chemotherapeutic drugs. Mutations and genome rearrangements also fuel the evolution of pathogenic microbes allowing them to escape the immune system, and to develop resistance to antibiotics. For many decades, remodeling of the genome (“nature”) was presumed to occur randomly and independently of environmental conditions (“nurture”). Dr. Rosenberg’s group studies a process that contradicts this view: mutation and genome rearrangement provoked by environmental stress to cells. They have discovered that under stress conditions, a special mistake-prone DNA copying enzyme is produced by cells, and the errors it makes lead to high levels of mutation. Some of the mutations allow the cells to thrive in the previously stressful environment. The cells studied are those of a model organism, the bacterium E. coli. However the error-prone enzyme is a member of a newly discovered superfamily of DNA copying enzymes present in all branches of the tree of life. The action of the four similar enzymes in humans, and similar enzymes in human pathogens, is likely to be important in human cancers, and to microbial pathogenesis. Dr. Rosenberg’s group, in collaboration with Dr. Philip Hastings at Baylor College of Medicine, has also discovered a second kind of environmentally provoked genome remodeling: adaptive gene amplification. Potentially highly relevant to cancer evolution, this is a stress-provoked expansion in the numbers of copies of a gene in cells, the outcome of which is cell growth in the stressful environment.

Dr. Rosenberg’s nomination was based on the following publications:

Hastings PJ, Bull HJ, Klump JR, Rosenberg SM." Adaptive amplification: an inducible chromosomal instability mechanism. ". Cell. 2000 Nov 22;103(5):723-31.

McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM. " SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. ". Mol Cell. 2001 Mar;7(3):571-9.