Identification of Saccharomyces cerevisiae Genes Whose Deletion Causes Synthetic Effects in Cells with Reduced Levels of the Nuclear Pif1 DNA Helicase.

TitleIdentification of Saccharomyces cerevisiae Genes Whose Deletion Causes Synthetic Effects in Cells with Reduced Levels of the Nuclear Pif1 DNA Helicase.
Publication TypeJournal Article
Year of Publication2015
AuthorsStundon, JL, Zakian, VA
JournalG3 (Bethesda)
Volume5
Issue12
Pagination2913-8
Date Published2015 Oct 19
ISSN2160-1836
KeywordsDNA Damage, DNA Helicases, DNA Replication, Epistasis, Genetic, Gene Deletion, Gene Expression Regulation, Fungal, Genes, Lethal, Phenotype, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Abstract

<p>The multifunctional Saccharomyces cerevisiae Pif1 DNA helicase affects the maintenance of telomeric, ribosomal, and mitochondrial DNAs, suppresses DNA damage at G-quadruplex motifs, influences the processing of Okazaki fragments, and promotes breakage induced replication. All of these functions require the ATPase/helicase activity of the protein. Owing to Pif1's critical role in the maintenance of mitochondrial DNA, pif1Δ strains quickly generate respiratory deficient cells and hence grow very slowly. This slow growth makes it difficult to carry out genome-wide synthetic genetic analysis in this background. Here, we used a partial loss of function allele of PIF1, pif1-m2, which is mitochondrial proficient but has reduced abundance of nuclear Pif1. Although pif1-m2 is not a null allele, pif1-m2 cells exhibit defects in telomere maintenance, reduced suppression of damage at G-quadruplex motifs and defects in breakage induced replication. We performed a synthetic screen to identify nonessential genes with a synthetic sick or lethal relationship in cells with low abundance of nuclear Pif1. This study identified eleven genes that were synthetic lethal (APM1, ARG80, CDH1, GCR1, GTO3, PRK1, RAD10, SKT5, SOP4, UMP1, and YCK1) and three genes that were synthetic sick (DEF1, YIP4, and HOM3) with pif1-m2. </p>

DOI10.1534/g3.115.021139
Alternate JournalG3 (Bethesda)
PubMed ID26483010
PubMed Central IDPMC4683662
Grant ListF30 AG042217 / AG / NIA NIH HHS / United States
GM26938 / GM / NIGMS NIH HHS / United States
R37 GM026938 / GM / NIGMS NIH HHS / United States
F30AG042217 / AG / NIA NIH HHS / United States
R01 GM026938 / GM / NIGMS NIH HHS / United States
R35 GM118279 / GM / NIGMS NIH HHS / United States