Kerr, Gary W. (2013) The role of protein phosphatase PP2ACdc55 during meiosis in Saccharomyces cerevisiae. PhD thesis, University of Warwick.

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Abstract

Meiosis is a specialised cell division that results in the formation of four genetically
unique haploid daughter cells from one diploid parent cell. This is achieved by one
round of DNA replication followed by two rounds of nuclear division. This is in
contrast to mitosis, which produces genetically identical diploid daughter cells.
Errors during meiosis can result in aneupolidy. In humans, aneuploidy can cause
miscarriage and disease such as Patau, Edwards and Down syndromes (trisomies 13,
18 and 21, respectively). Therefore, understanding how meiosis is regulated is of
great importance in understanding the causes of aneuploidy and disease in humans.
In this thesis, I have used the model organism budding yeast to study how meiosis is
regulated in yeast cells, with a view to understanding how meiosis is regulated in
human cells.
PP2ACdc55 is a highly conserved phosphatase and its role in meiosis was not
addressed in any organism before my work. I constructed a meiotic null allele of
CDC55 (cdc55-mn) by replacing its promoter with the mitosis-specific PCLB2. By
carefully characterising the phenotype of cdc55-mn strains, I showed PP2ACdc55 is
crucial for timing the activation of the FEAR network. I have demonstrated that
premature activation of FEAR during meiosis (caused by a lack of PP2ACdc55
activity) blocks spindle assembly and nuclear divisions. In cdc55 meiotic null
(cdc55-mn) cells, the Cdk-counteracting phosphatase Cdc14 is prematurely released
from the nucleolus concomitant with hyperphosphorylation of Net1. I have found
that a mutant form of Net1 that lacks 6 of the Cdk phosphorylation sites rescues the
meiotic null defect of cdc55-mn cells. Therefore, I have shown that
phosphoregulation of Net1 by PP2ACdc55 is essential in order to prevent precocious
exit from meiosis I.
In my work described in Chapter 4, I isolated mutant alleles of cdc55 that suppressed
the spo12Δ dyad phenotype confirming the opposing roles of Net1-phosphorylation
by Cdc55 and Spo12 in the FEAR pathway. I also isolated alleles of CDC55 that
suppressed the spo11Δ spo12Δ spore lethality. These alleles affected reductional
segregation during meiosis I in achiasmate cells but had no effect in wild type cells.
Investigating these alleles further might shed insights into mechanisms that work
with chiasmata in ensuring efficient monopolar attachment during meiosis I.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QK Botany Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Phosphatases, Meiosis, Saccharomyces cerevisiae
Official Date:	December 2013
Dates:	Date Event December 2013 Submitted
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Arumugam, Prakash
Sponsors:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)
Extent:	1 volume (various pagings) : illustrations, charts.
Language:	eng

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