Date of Degree

5-2015

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Hualin Zhong

Subject Categories

Biology

Abstract

The nuclear pore complexes (NPCs) are large multi-protein channels that traverse the nuclear envelope and mediate nucleo-cytoplasmic transport. Proteomic studies have revealed that NPCs are composed of about thirty different proteins called nucleoporins. I explored a particular nucleoporin, Nup211, in fission yeast. nup211 is an essential gene; its deletion is lethal and causes morphological defects. In this study, I characterized the cell morphological defects caused by the down-regulation of Nup211 and found that restoring the N-terminal domain of Nup211 was sufficient to rescue the lethal phenotype and partially suppress the morphological defects. Additionally, I investigated the role Nup211 plays in cytokinesis. RNA-Sequencing analysis revealed that Nup211 down-regulation and overexpression elicited a global change in gene expression. Specifically in Nup211-down-regulated cells, there was a decrease in ace2 gene expression and its downstream targets- adg1, adg2, adg3, mid2, cfh4, eng1, agn1 and rgf3. ace2 and its target genes play a dominant role in normal septum formation, dissolution, and cell separation (cytokinesis). I show that directly restoring ace2 expression significantly suppressed the morphological defects caused by Nup211 down-regulation. These results suggest that Nup211 partially controls cytokinesis through control the expression of ace2. Furthermore, we identified proteins important for cytokinesis, such as actin, were affected by Nup211 down-regulation. Taken together, our data indicate that Nup211 is fundamental for fission yeast cell shape maintenance, cytokinesis and global gene expression.

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