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Dissertation Information for Jennifer Downs

NAME:
- Jennifer Downs

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2005)

ADVISORS:
- Debra L. Mohler

COMMITTEE MEMBERS:
- David G. Lynn
- Justin P. Gallivan

MPACT Status: Fully Complete

Title: Organometallic photonucleases. I. DNA cleavage by the photolysis of cyclopentadienyl metal complexes: Mechanistic studies and sequence selectivity of strand scission by CpW(CO)3CH3. II. Footprinting of chromatin structure and chromatin remodeling by SWI/SNF utilizing CpW(CO)3CH3. III. Dual mechanisms of DNA damage by MoX(eta3-allyl)(CO)3(phen) complexes

Abstract: The photolysis of CpW(CO) 3 CH 3 has been shown to produce methyl radicals and to cleave DNA in a single-stranded manner, and preliminary evidence implicated a carbon-centered radical in this process. In this work, the mechanism of strand scission in this reaction was determined to occur by hydrogen atom abstraction from the 4\'- and 5\'-positions of the deoxyribose moiety of the backbone of DNA. Additionally, in a side reaction that does not lead to frank strand scission, all four bases of DNA are methylated under these conditions; however, none of these base or backbone modifications lead to the formation of abasic sites. Given the ideal characteristics of CpW(CO) 3 CH 3 as a footprinting agent, it was utilized in footprinting studies to determine the higher order packing of nucleosomes in chromatin as well as to determine the structural changes that occur during chromatin remodeling by the SWI/SNF complex. While this reagent shows promise as a footprinting agent, more studies are needed to fine-tune the footprinting reaction. In addition, dual mechanisms of DNA damage are reported for MoX(รง 3 -allyl)(CO) 2 (phen) complexes, where X = H or X = CH 3 . These complexes have been shown to cleave DNA in a single-stranded fashion non-sequence specific fashion via hydrogen atom abstraction from the H1\' and/or the H5\' of the deoxyribose moiety. In addition a G-selective DNA cleavage mechanism is observed under non-irradiated conditions. The products of this cleavage have been observe to be methylguanine, 8-methoxyguanine, and 8-oxo-guanine, as determined by mass spectral analysis.

MPACT Scores for Jennifer Downs

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-03-22 15:57:50

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