Induction and processing of complex DNA damage in the BRCA1-deficient human breast cancer cell line, HCC1937 / by Jessica Hair.
| Author/creator | Hair, Jessica author. |
| Other author | Georgakilas, Alexandros G., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 2008. |
| Description | 72 leaves : illustrations (some color) ; 29 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | DNA damage and oxidatively induced stress has been associated with cancer. Oxidative cluster DNA lesions (OCDLs) are two or more closely spaced DNA lesions within a short DNA fragment of 1-10 base pairs on opposing DNA strands. Double strand breaks (DSBs) and non-DSB bistranded oxidatively induced clustered DNA lesions are complex DNA damages that are hypothesized to be repair resistant and to challenge the repair mechanisms of the cell. Studies have shown that a lower fidelity or deficiencies in repairing OCDLs promote mutagenesis and carcinogenesis. This study has evaluated the processing of DSBs and OCDLs in BRCA 1-deficient HCC1937 cells and HCC1937 cells with partially restored BRCA1 after exposure to low doses of ionizing radiation. Comparison has been also performed with the human breast cancer cells MCF7 and nontumorigenic MCF-10A cells. For the detection of oxidative DNA damage adaptations of pulse field and single cell gel electrophoresis have been used as well the analysis of [gamma]H2AX foci. In addition. Western blotting techniques were used for the detection of BRCA1 expression. HCC1937 cells have a significant difficulty in processing DSBs and oxybase clusters compared to MCF-7 cells (partially compromised BRCA1) and HCC1937 with BRCAL Given that HCC1937 cells harbor a C-terminally truncated BRCA1, this concludes that BRCA1 has involvement in other repair pathways expect DSB repair and it is also involved in the repair of oxidative DNA lesions. Our studies underline the importance of BRCA1 repair protein especially in the case of lack or reduced expression occurring in many cases of familial or sporadic breast cancer. |
| General note | Presented to the faculty of the Department of Biology. |
| General note | Advisor: Alexandros G. Georgakilas |
| Dissertation note | M.S. East Carolina University 2008 |
| Bibliography note | Includes bibliographical references (leaves 70-72). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | Access Content Online | ✔ Available |