Find results with:

Add another field

Search by date

to

Searching collections:

Dartmouth Dissertations

Add or remove collections

Home Dartmouth Dissertations george2010 1

Reference URL

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Functional analysis of cell cycle genes by genome-wide expression data and meta-analysis of RNAi screens.

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Call No.	Ph.D. 2010
Author	George, Lacy K.
Title	Functional analysis of cell cycle genes by genome-wide expression data and meta-analysis of RNAi screens.
Date	2010
Abstract	Successful traversal of the cell division cycle is paramount for maintaining a cell's genomic integrity and fitness. To ensure the faithful replication and segregation of the genome, cellular components, and cytoplasm, eukaryotes have evolved a complex cell cycle, with layers of regulation and built-in checkpoints. Disruption of any of these processes can be catastrophic for the cell or organism, often resulting in deleterious mutations or cell death. As deletion/improper activation of key regulatory proteins has been shown to be involved in tumorigenesis, a full understanding of the cell cycle machinery is of vital importance. The work presented here seeks to investigate the cell cycle using three different methods. First, I used existing cell cycle data to further investigate the function of the gene FAM64A, which I hypothesized would play a role in maintaining or establishing the mitotic spindle. Fam64A was identified as showing peak mRNA expression in G2/M phase in genome-wide expression data; I further showed that the protein was also cell cycle-regulated, and was degraded by the proteasome at the end of mitosis. I report that the knockdown of Fam64A by siRNA results in monopolar spindles. Functionally, Fam64A interacts with members of the Chromosomal Passenger Complex (CPC) and other key mitotic regulators in vivo. I also sought to identify the full complement of cell cycle-regulated genes in an untransformed cell line, Immortalized Mammary Epithelial Cells (IMECs). While there exist studies identifying cell cycle-regulated genes, often these are performed in tumor-derived cell lines, and here I report that the genes identified as cell cycle-regulated in IMECs are quite divergent from those reported in HeLa cells, suggesting that genes required for cell cycle progression may vary between cells of different lineages and transformation status. Finally, I performed a meta-analysis of existing large-scale and genome-wide screens for genes required for cell cycle progression. I found that the overlap between four published screens was very small, with only Polo-like kinase 1 being identified as having a cell cycle phenotype in all four screens. This underscores the need for more of such screens using a variety of cell lines and techniques. With the collation of many similar screens, I may achieve a much more complete understanding of the many proteins required for cell cycle progression, and with that, perhaps future targets for cancer therapies.
Description	1 online resource (xiii, 148 leaves) : illustrations (some color)
Format	application/pdf
Advisor	Whitfield, Michael L. ; Compton, Duane ; Moore, Jason ; Pelletier, Laurence
Subject	Cell cycle -- Regulation. ; Genetic regulation. ; Small interfering RNA. ; Spindle (Cell division). ; Epithelial cells -- Genetic aspects. ; Mammary glands -- Cytology. ; Cell lines. ; Cell Cycle -- genetics. ; Genes cdc. ; RNA Interference. ; Mitotic Spindle Apparatus -- genetics.
College	Dartmouth Medical School -- Department of Genetics.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D)--Dartmouth College.
Copyright	In Copyright. This material is protected by copyright and/or related rights. You are free to use this material in any way that is permitted by copyright law that applies to your use. For other uses, you need to obtain permission from the rights-holder(s). http://rightsstatements.org/page/InC/1.0/
DOI	https://doi.org/10.1349/ddlp.3099

Title	george2010 1
Full Text	FUNCTIONAL ANALYSIS OF CELL CYCLE GENES BY GENOME-WIDE EXPRESSION DATA AND META-ANALYSIS OF RNAI SCREENS A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genetics by Lacy K. George DARTMOUTH COLLEGE Hanover, New Hampshire 15 July, 2010

Find results with:

Searching collections:

Home Dartmouth Dissertations george2010 1

Functional analysis of cell cycle genes by genome-wide expression data and meta-analysis of RNAi screens.

Object Description

Description

Functional analysis of cell cycle genes by genome-wide...

Functional analysis of cell cycle genes by genome-wide...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12