The Role of Pre-Replication Complex Proteins in Drosophila Ovarian Stem Cell Maintenance and Proliferation

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

Justin R Safin (Creator)

Institution

East Carolina University (ECU )

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

Abstract: Cancer stem cells (CSCs) may hold the key to advances in cancer research. Like adult tissue-specific stem cells , CSCs are able to self-renew and last a lifetime. These shared characteristics can thus be used to help learn more about CSCs and how they work. More specifically , understanding the molecular mechanisms that control adult tissue-specific stem cell proliferation can lead to better regenerative therapies and a better understanding of CSCs overall. The proliferation of Drosophila ovarian germline stem cells (GSCs) , as well as their ability to create differentiated daughters , relies on proper DNA replication. By investigating the regulation of stem cell division , we can advance our knowledge of the fine line between regulated versus unregulated division , and the causes behind each. One of the major components of replication control are the pre-initiation complex (PIC) proteins , which are essential for proper DNA replication. For example , Minichromosome maintenance protein 10 (MCM10) is recruited during the transition from G1 to S-phase , and aids in the recruitment of other PIC proteins to the replication fork. To investigate whether PIC proteins are essential for stem cell function , two comparisons were made. The average number of GSCs per germarium in control and mutant flies were compared. Next EdU staining was utilized to calculate the percentage of GSCs that were in S-phase. Once again , control and mutant percentages were compared to determine if MCM10 mutants affect stem cell function. We demonstrate that the loss of MCM10 results in a reduction in stem cell number and an increase S-phase length which is an indication of an altered cell cycle. Ongoing studies are investigating if stem cell loss in MCM10 mutants is due to DNA damage and to observe the effects of other pre-replication initiation complex mutant proteins. Combined , our data suggests that PIC proteins are critical for stem cell function.

Additional Information

Publication

Thesis

Language: English

Date: 2017

Keywords

Stem cells, Drosophila, germline stem cells, MCM10, fruit fly, cancer stem cells, honors thesis

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