Evaluating The Essential Functions Of The Replication Factor Mcm10 In Drosophila Melanogaster

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Michael C. Reubens (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Often referred to as miraculous, life as we know depends not upon miracles but on a series of highly orchestrated and regulated biochemical processes collectively known as the cell cycle. It is through these series of highly monitored stages that cells are able to grow, divide, and accurately transmit their genetic blueprint into their progeny. An underlying process of the cell cycle, termed the chromosome cycle, begins with accurate replication of the genome, followed by condensation of the newly synthesized nucleic acid into a DNA-protein complex known as chromatin, and ultimately the proper segregation of the resulting sister chromatids into the daughter cells. The chromosome cycle is of utmost importance for the maintenance of genome function and integrity, as well as preservation of cellular identity. Errors during any stage of these key processes can manifest as genetic diseases, cancers, developmental abnormalities, or death. Of the many proteins involved in these essential processes, mini-chromosomal maintenance protein 10 (Mcm10) is a protein that has recently received increased attention due to evidence suggesting that it functions in multiple steps of the chromosome cycle. Since its discovery in S. cerevisiae Mcm10 has been suggested to play a role in the activation and elongation phases of DNA replication, has been shown to function in chromatin dynamics, and recently has been demonstrated to interact with multiple members of common DNA damage repair pathways. Previous analyses in our lab utilizing two mutant alleles in D. melanogaster validated that Mcm10 functions in both DNA replication and the formation of chromatin states. To further investigate the essential nature of this conserved eukaryotic replication factor in a multicellular system, we have established a collection of 20 mutant alleles in Drosophila. Analysis of these alleles indicated that Mcm10 is required for early embryogenesis and oogenesis\; however, it is dispensable for adult viability. Our analyses also suggest that the expanded C-terminal domain present in D. melanogaster is involved in the formation of heterochromatin and chromosome condensation, further validating a role for this protein in maintaining genomic stability. Taken together the results of this study bring into question the essential nature of Mcm10 in all cell types, and demonstrate the importance of studying cell biology in multicellular systems. Furthermore, these results demonstrate the utility of our mutant collection to further investigate the tissue specific functions of Mcm10 in replication and chromatin dynamics.

Additional Information

Publication

Dissertation

Language: English

Date: 2023

Subjects

Biology;Developmental biology;Genetics;Chromatin dynamics;Embryogenesis;Genome stability;Maternal effect;Oogenesis

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