Dissertation/Thesis Abstract

p53 and Beclin 1 in Caenorhabditis elegans are involved in cell death and DNA damage repair
by Gamss, Sandy, Ph.D., City University of New York, 2013, 124; 3561215
Abstract (Summary)

p53 is a key regulator of growth arrest, DNA repair, apoptosis, and autophagy in response to cellular stress in animals as diverse as Caenorhabditis elegans and humans. In mammals, p53 functions as a key tumor suppressor protein that promotes removal of potentially tumorigenic cells. p53 is mutated or deleted in over 50% of all mammalian tumors and these tumors are highly resistant to available therapies. Therefore, identifying therapeutic agents and cell death pathways that promote p53-independent cell death is vital to the future of cancer therapy. We are interested in identifying how the alkylating agent, 10-decarbomyl mitomycin C (DMC) promotes p53-indpendent cell death. To answer this question, we used a C. elegans as a model system to identify known and novel cell death genes involved in DMC-induced death. C. elegans have an orthologue of p53, cep-1, that functions in germline cell death in a similar way to p53 in apoptosis. The germline in C. elegans has both mitotic and meiotic cells and displays CEP-1/p53-dependent cell death in response to UV. We examined both germline cell death and transcript levels of CEP-1 target genes in C. elegans. We found that DMC increased CED-1::GFP positive cells and DNA lesions in the absence of CEP-1 while UV required CEP-1 for germline cell death but not nuclear lesion formation. More lesions were seen over time in cep-1(gk138) mutant worms leading to the idea that CEP-1 is involved in DNA repair. Additionally, we examined the role of autophagy in cell death and DNA damage and saw that initially the knockdown of bec-1 required CEP-1 for increases in germ cell death. However in the F1 generation of bec-1 RNAi knockdown animals, the observed increase in cell death was due to a lack of clearance. Furthermore, bec-1 knockdown resulted in the increase of DNA lesions in worms with UV damage.

Indexing (document details)
Advisor: Bargonetti, Jill
Commitee: Loayza, Diego, Melendez, Alicia, Rockwell, Patricia, Shaham, Shai
School: City University of New York
Department: Biochemistry
School Location: United States -- New York
Source: DAI-B 74/09(E), Dissertation Abstracts International
Subjects: Molecular biology, Cellular biology, Biochemistry
Keywords: Beclin 1, Caenorhabditis elegans, Cell death, DNA damage repair, P53
Publication Number: 3561215
ISBN: 978-1-303-08187-3
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