Affiliation:
1. Department of Biochemistry and Molecular Genetics and Program in Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262 1 ;
2. Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York, New York 100162
3. Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham, New Hampshire 03824 3 ; and
Abstract
ABSTRACT
Yeast contains at least two complex forms of RNA polymerase II (Pol II), one including the Srbps and a second biochemically distinct form defined by the presence of Paf1p and Cdc73p (X. Shi et al., Mol. Cell. Biol. 17:1160–1169, 1997). In this work we demonstrate that Ccr4p and Hpr1p are components of the Paf1p-Cdc73p-Pol II complex. We have found many synthetic genetic interactions between factors within the Paf1p-Cdc73p complex, including the lethality of
paf1Δ ccr4
Δ,
paf1Δ hpr1
Δ,
ccr4Δ hpr1
Δ, and
ccr4Δ gal11
Δ double mutants. In addition,
paf1
Δ and
ccr4
Δ are lethal in combination with
srb5
Δ, indicating that the factors within and between the two RNA polymerase II complexes have overlapping essential functions. We have used differential display to identify several genes whose expression is affected by mutations in components of the Paf1p-Cdc73p-Pol II complex. Additionally, as previously observed for
hpr1
Δ, deleting
PAF1
or
CDC73
leads to elevated recombination between direct repeats. The
paf1
Δ and
ccr4
Δ mutations, as well as
gal11
Δ, demonstrate sensitivity to cell wall-damaging agents, rescue of the temperature-sensitive phenotype by sorbitol, and reduced expression of genes involved in cell wall biosynthesis. This unusual combination of effects on recombination and cell wall integrity has also been observed for mutations in genes in the Pkc1p-Mpk1p kinase cascade. Consistent with a role for this novel form of RNA polymerase II in the Pkc1p-Mpk1p signaling pathway, we find that
paf1Δ mpk1
Δ and
paf1Δ pkc1Δ
double mutants do not demonstrate an enhanced phenotype relative to the single mutants. Our observation that the Mpk1p kinase is fully active in a
paf1
Δ strain indicates that the Paf1p-Cdc73p complex may function downstream of the Pkc1p-Mpk1p cascade to regulate the expression of a subset of yeast genes.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
129 articles.
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