One of the hallmarks of cancer cells is loss of control of the cell cycle, leading to uncontrolled cellular division. Paramount to understanding the mechanisms involved in the uncontrolled proliferation of cancer cells is understanding the mechanisms that control cell division. The objectives of this proposal are to analyze genes which were identified as extragenic suppressor of nimXcdc2 mutations in the filamentous fungus Aspergillus nidulans. nimXcdc2 controls both the G1/S and G2/M transitions of the nuclear division cycle of A. nidulans. Extragenic suppressors of mutations in nimXcdc2 are likely to encode proteins which interact with the NIMXcdc2 protein and are important in these transitions or in other processes controlled by nimXcdc2. Previous work has identified several suppressers, three of which will be analyzed in this study. These are snxA, snxB, and snxC, for suppressor of nimX. Mutation of snxA leads to a reversible block in G1 of the cell cycle; this is only the second gene identified in A. nidulans to lead to a G1-speak block. The snxB mutation causes increased septation and branching and decreased cell size, while the snxC mutation causes defects in the development of asexual conidiospores. These three suppressors thus involve three different aspects of the biology of A. nidulans which are affected by nimXcdc2: nuclear division, septation, and conidiation. In these conditions, snxA will be cloned and sequenced and the snxB and snxC mutations will be analyzed phenotypically and genotypically to determine more specifically their effects on the cells. These experiments will provide new information on the molecular mechanisms involved in normal cell division and may therefore impact the study of disease of cell proliferation, such as cancer.
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