Abstract

Magnetite nanoparticles particulate matter pollution is escalating in large cities like New Mexico, Manchester city, Cairo, and New Delhi. Combustion derived Magnetite nanoparticles was found deposited in internal vital organs of deceased residents of urban areas. A great deal of research focused on the genotoxic and cytotoxic effects of Magnetite Nanoparticles (MNPs). In our work we focus on the mechanisms employed in DNA repair of higher chromatin structures. We employed the sensitive analysis of anti γ-H2AX to detect and monitor the repair of DSBs following exposure to MNPs. A 2- fold delay in the repair of heterochromatin associated DSBs in comparison with euchromatin was detected. The slow repairing heterochromatin γ-H2AX foci were found almost exclusively at the peripheries of the chromocenters, marking the physical barrier that the compacted chromatin impose on the extension of the DNA repair signal. The heterochromatin associated DSBs constituted 10.3% of the original DSBs initially introduced, similarly the fraction of DSBs that requires ATM for DNA repair constitutes about 10-25%. No visible structural changes happened in heterochromatin chromocentres during the repair. On Inhibition of ATM a repair defect in the heterochromatin DSBs was evident post exposure to MNPs, comparable to the repair defect imparted after exposure to Neocarzinostatin (NCS). This repair defect could not be compensated by other PIKKs (ATR and DNA PKcs). Therefore, ATM is essential for the transient relaxation of the nucleosome to allow the extension of the DNA repair machinery. Individuals lacking a functional ATM protein, will lack the ATM dependent chromatin relaxation and extension of repair machinery. So, they would be prone to accumulate mutations in the repetitive satellite pericentromeres, centromeres and telomeres, imparting a MNPs sensitivity to those individuals.

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Graduation Date

Fall 9-13-2020

Submission Date

September 2020

First Advisor

Kakarougkas, Andreas

Second Advisor

NA

Third Advisor

NA

Committee Member 1

Gad, Mohamed Zakaria

Committee Member 2

Abdelnaser, Anwar

Committee Member 3

Zada, Suher; Kakarougkas, Andreas

Extent

81 p.

Document Type

Master's Thesis

Library of Congress Subject Heading 1

Biotechnology

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known.

Institutional Review Board (IRB) Approval

Not necessary for this item

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