Kendrick Yim

EXPLORING THE EFFECTS AND MECHANISM OF THE CEP-1 TUMOR SUPPRESSOR ON CHROMOSOME NONDISJUNCTION IN C.ELEGANS

The p53 tumor suppressor is the most frequently mutated gene in cancer. In response to genomic damage, p53 promotes DNA repair, cell cycle arrest, or in cases of extreme damage, programmed cell death. p53 is critical in maintaining chromosome stability. Genomic instability, manifested as chromosome nondisjunction, or improper chromosome segregation, is a hallmark feature of cancer cells. Since all human tumors contain chromosomal aberrations, understanding the mechanisms through which p53 acts to maintain proper chromosome function is fundamental to improving cancer diagnostics, prognostics, and therapeutics. The p53 homologue, CEP-1, in C. elegans is utilized as a model due to its highly conserved DNA binding domain and overall 3-D crystal structure demonstrating analogous function and evolutionary relatedness to human p53. Normal X chromosome nondisjunction occurs in C. elegans, as demonstrated by the presence of males (XO) in a largely hermaphroditic (XX) population. Typically this nondisjunction event occurs at 0.2%, while high incidence of males (Him) strains exhibit a 10-150 fold increase in male production. Varying expression levels of CEP-1 in various Him strains has allowed for the measurement of CEP-1’s impact and role in chromosome nondisjunction. My data suggest that CEP-1 is recruited to suppress X chromosome loss events, while the tumor suppressor’s impact on the autosomes is currently under study. Future studies of the exact mechanism by which CEP-1 acts will provide a more thorough understanding of p53’s function. This may ultimately lead to the development of new tools to detect cancer earlier and develop more effective drug therapies.