Date of Award

2015

Document Type

Open Access Thesis

Department

Biological Sciences

First Advisor

Alan Waldman

Abstract

Hutchinson-Gilford Progeria Syndrome is disease of highly accelerated aging. In addition to appearing physically old mere months after birth, patients suffer from maladies typical of the elderly, including heart attack and stroke, two factors which contribute to an average life expectancy of 14 years. The source of progeria has been identified as progerin, a defective variant of nuclear lamina protein lamin A. Progerin has also been found natively in healthy cells (concentration increasing with age), and is known to adversely affect nuclear morphology and chromosomal integrity. This thesis sought to investigate the effect of progerin upon which pathways were favored in the repair of DNA double-strand breaks. Plasmids were engineered for use in the creation of cell lines inducible for progerin expression. In addition, immortalized human fibroblast cells were transfected to express progerin constitutively. These cells were assayed for the relative rates of different modes of repair after spontaneous and double-strand break-induced recombination. It was discovered that the progerin-expressing cells repair damage via non-homologous end joining at a higher rate than control cells, though there are significant caveats to these data.

Included in

Biology Commons

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