Psf2 a member of the heterotetrameric GINS Complex plays a role in cell cycle progression and maintenance of genomic integrity

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

Laura M. Henderson (Creator)

Institution

East Carolina University (ECU )

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

Advisor

Tim Christensen

Abstract: Multiple proteins are involved in the complete and accurate replication of the genome during S phase of the cell cycle. At the G1/S phase transition the heterotetrameric GINS complex is recruited to the origin and facilitates the helicase activity of the Mcm2-7 complex. Each of the four subunits of the GINS complex is essential for proper completion of DNA replication initiation and elongation. Inaccurate replication of the genome results in a multitude of disease states specifically cancer. Psf2 a subunit of the GINS complex has been previously implicated in the segregation of chromosomes during M phase. Additionally it has been shown that reduced levels of Psf2 in yeast results in stalled replication forks and incomplete DNA replication. However to date the function of Psf2 in higher eukaryotes has only been studied in tissue culture models. To provide insight into the role of Psf2 in a multicellular organism we used an in vivo approach to characterize the phenotypes resulting from the C-terminal truncation of Psf2 in a homozygous lethal mutant in Drosophila. Through analysis of larval brain tissue salivary tissue ovarioles and embryonic tissue we found the mutant Psf2 displays defects during M phase of the cell cycle and DNA replication in endoreplicating cells. Curiously the RNAi knockdown of Psf2 results in a defect in S phase of the cell cycle with no effects on M phase. Therefore we hypothesize that Psf2 plays an essential role in cell cycle progression. Additionally removal of the C-terminal domain is essential for either the correct formation of the GINS complex or for an external interaction possibly with checkpoint or chromosome segregation proteins. 

Additional Information

Publication

Thesis

Date: 2011

Keywords

Biology, Molecular, Biology, Cell

Subjects

Genomics

Genomes

Proteins

DNA replication--Regulation

Cell cycle--Regulation

Eukaryotic cells

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