Mitotic chromosome phenotypes associated with a panel of Mcm10 mutants in Drosophila. Ritu Dalia, Michael Reubens, Tim W. Christensen. Biology Dept, East Carolina University, Greenville, NC.

   Replication of the genome and proper formation, and packaging, of chromatin are processes essential to eukaryotic life. Maintenance of epigenetic chromatin states is essential for faithfully reproducing the transcriptional state of the cell; likewise, replication of DNA with high fidelity is crucial for accurate passage of genetic information from a cell to its progeny. Defects in DNA replication and improper regulation of the chromatin states can result in genome instability which can manifest as disease, or death of the organism. There are a plethora of factors involved in the process of DNA replication in eukaryotes, and recent studies have shed light on one of the factors called mini-chromosome maintenance 10 (Mcm10) as an essential DNA replication factor. First discovered in S. cerevisiae, Mcm10 is an abundant nuclear protein that has been implicated in the activation of the Pre-RC, interacts with members of the elongation machinery such as Pol, and has recently been shown to be required in the formation of heterochromatin in both yeast and Drosophila. Previous analysis of two Drosophila Mcm10 mutant alleles demonstrated that Mcm10 not only plays a role in DNA replication, but also has a role in heterochromatic silencing and chromosome condensation. To further investigate the roles of Mcm10 we used a collection of over 20 missense mutations generated using a Tilling approach. Mitotic index data generated shows that there is not enough evidence to show a significant mitotic delay in the mutant strains. Interestingly though, varying types of chromosomal phenotypes, such as severe condensation defects, separated sister chromatids, aneuploidy and anaphase bridge defects, were observed in these mutants suggesting that Mcm10 is involved in maintaining the genomic stability. Further evaluation of these mutants will help elucidate the biological functions of this well conserved protein as well as provide information on the domains of the protein required for its different biological functions.