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The role of benedict in Drosophila cell cycle regulation

$217,670R15FY2005GMNIH

Fordham University, Bronx NY

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Abstract

DESCRIPTION (provided by applicant): My laboratory's long-term goal is to improve our understanding of cell cycle regulation during Drosophila development. This proposal focuses on the molecular identification and functional characterization of benedict (bene), a gene identified in a clonal screen I carried out as a post-doctoral fellow. The three known loss-of-function mutations in bene are lethal and disrupt endoreplication in the larval fat body and salivary gland, bene germ line clones exhibit nurse cell chromosome condensation defects and disruption of nurse cell endoreplication. The morphology of oocyte chromosomes in these clones is characteristic of meiotic disruption defects, bene mutations are not cell lethal and do not cause obvious mitotic defects. The suite of bene defects suggests that bene may play a unique role in endoreplication and meiotic cell cycle regulation, and mutations that disrupt M phase regulation, S phase regulation, and translation regulation in oocytes all exhibit different subsets of the bene phenotypes. We have mapped bene to a 300 kb, sequenced region of the genome that includes 31 candidate genes. Specific Aim 1: To identify which of the 31 candidate genes in the bene region is disrupted in the mutant bene alleles and to determine the bene expression pattern\ Specific Aim 2: To analyze bene function in the larva and ovary by analysis of cell cycle markers and by assays for genetic interaction with cell cycle regulators.

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