A Tale of Two Projects: Basis for Centrosome Amplification after DNA Damage and Practical Assessment of Photodamage in Live-Cell Imaging: A Dissertation

作者: Stephen Douthwright

DOI: 10.13028/M2RP5R

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摘要: This thesis comprises two separate studies that focus on the consequences of cellular damage. The first investigates effects DNA damage centriole behavior and second characterizes phototoxicity during live-cell imaging. Cancer treatments such as ionizing radiation and/or chemotherapeutic damaging agents are intended to kill tumor cells, but they also normal proliferating cells. Although centrosome amplification after is a well-established phenomenon for transformed it not fully understood in untransformed presence extra centrosomes cell populations raises chances genomic instability, thus posing additional threats patients undergoing these therapies. I characterized synchronized (RPE1) human Treatment with radiomimetic drug, Doxorubicin, prolongs G2 phase by at least 72hrs, where 52% cells display disengaged centrioles 10% contain centrioles. disengagement mediated Plk APC/C activities both singly combination. Disengaged associated maturation markers suggesting capable organizing spindle poles. Despite high incidence disengagement, only small percentage reduplicate due p53/p21 dependent inhibition Cdk2 activity. all become prolonged phase, 14% eventually go through mitosis, which 26% or

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