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Jacqueline Segall
Professor
B.Sc., McGill University, 1972
Ph.D., Harvard University, 1977
Washington University, 1977-80 |
Medical Sciences
Building, Room 5336
416-978-4981
j.segall@utoronto.ca |
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Regulation of Gene Expression
Research Synopsis
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Regulation
of gene expression during sporulation in S. cerevisiae:
We are investigating the molecular mechanisms involved
in regulating gene expression during development. The
sporulation program in yeast provides a simple model system
for such studies. The process of spore formation, initiated
on starvation of a diploid cell, involves a coordinated
series of genetic, biochemical, and morphological events
that generate a tetrad of hardy, dormant spores. This
orderly program depends on the sequential activation of
temporally distinct subsets of genes.
Our early studies led to the identification of the premiddle,
middle, mid-late and late classes of sporulation-specific
genes. After characterization of the promoter elements
of several of these genes, we identified transcriptional
regulatory molecules that bind to these sites. Currently,
we are using genetic and biochemical approaches to elucidate
the molecular mechanisms by which these proteins control
the transcriptional cascade of gene expression through
sporulation.
Temporal program of gene expression during sporulation.
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One of the regulatory
molecules that we are studying, called Ndt80, acts as
a global activator of middle genes. The expression of
the NDT80 gene and the activity of the Ndt80 protein
are tightly regulated. A sporulation-specific checkpoint
mechanism, which is activated when there is a delay in
preparing chromosomes for the meiotic divisions, targets
several regulatory molecules, including Nd80, for inactivation.
Because Ndt80 activates expression of genes that are responsible
for driving cells into the meiotic divisions, activation
of this checkpoint causes cells to arrest before they
attempt to segregate the defective chromosomes. We are
currently studying the signal transduction pathway that
leads to inactivation of Ndt80. We know that the ability
of Ndt80 to activate gene expression is modulated by phosphorylation.
Thus, we searching for kinases that directly modify Ndt80.
During our analysis of the mid-late class of genes that are involved in spore wall formation, we discovered that a negative regulatory system prevents expression of these genes in growing cells. We are currently elucidating the role of Rim101, a DNA-binding protein that we identified in a genetic screen, in the assembly of a multi-factor repression complex.
Role of yeast Transcription Factor III A in the assembly
of a transcription complex on the yeast 5S RNA gene:
Recruitment of eukaryotic RNA polymerases to the start
site of transcription requires several accessory transcription
factors. We are studying the role of yeast TFIIIA in the
sequential assembly of a multi-factor TFIIB-TFIIIC-TFIIIA
complex on the 5S RNA gene. We first studied the interaction
of TFIIIA with the promoter region of the 5S RNA gene,
which is the first step in the assembly of the transcription
complex. Detailed alanine-scanning mutational analyses
have identified two distinct regions of TFIIIA that appear
to be critical for the next assembly step: recruitment
and proper docking of TFIIIC. We are currently studying
the protein-DNA and protein-protein interactions that
contribute to the formation of a functional transcription
complex.
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Meiotic recombination checkpoint
(dmc1 cells) |
Selected Publications
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Components of the ESCRT Pathway, DFG16, and YGR122w Are Required for Rim101 to Act as Corepressor with Nrg1 at the Negative Regulatory
Element of the DIT1 Gene of Saccharomyces cerevisiae . K. Rothfels,
J. Tanny, E. Molnar, H. Friesen, C. Commisso and J. Segall (2005)
Mol. Cell. Biol. 25, 6772-6788.
Activity of phosphoforms and truncated versions of Ndt80, a
checkpoint-regulated sporulation-specific transcription factor of
Saccharomyces cerevisiae.
G. Shubassi, N. Luca, J. Pak and J. Segall (2003) Mol Gen Genomics 270, 324-336.
Regulation of
the premiddle and middle phases of expression of the NDT80
gene during sporulation of Saccharomyces cerevisiae.
J. Pak and J. Segall (2002) Mol. Cell. Biol. 22, 6417-6429.
Role of Ndt80, Sum1, and Swe1 as targets of the meiotic
recombination checkpoint that control exit from pachytene
and spore formation in Saccharomyces cerevisiae.
J. Pak and J. Segall (2002) Mol. Cell. Biol. 22, 6430-6440.
NTD80 and the meiotic recombination checkpoint regulate expression of middle sporulation-specific gene in Saccharomyces cerevisiae. S. R. Hepworth, H. Friesen, and J. Segall (1998) Mol. Cell. Biol. 18, 5750-5761.
A hydrophobic segment within the 81-amino acid domain
of TFIIIA from Saccharomyces cerevisiae is essential
for its transcription factor activity. O. Rowland and
J. Segall (1998) Mol. Cell. Biol. 18, 420-432.
SPE3, which encodes spermidine synthase, is required for
maximal NREDIT-mediated repression in Saccharomyces
cerevisiae. H. Friesen, J. Tanny, and J. Segall. (1998)
Genetics 150, 59-73.
An Ssn6-Tup1-dependent negative regulatory element controls
sporulation-specific expression of DIT1 and DIT2 in Saccharomyces
cerevisiae. H. Friesen, S. Hepworth, and J. Segall
(1997) Mol. Cell. Biol. 17, 123-134. |
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