Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces cerevisiae

Abstract Changes in gene copy number contribute to genomic instability, the onset and progression of cancer, developmental abnormalities and adaptive potential. The origins of gene amplifications have remained elusive; however, DNA rereplication has been implicated as a source of gene amplifications. The inability to determine which sequences are rereplicated and under what conditions have made it difficult to determine the validity of the proposed models. Here we present Rerep-Seq, a technique that selectively enriches for rereplicated DNA in preparation for analysis by DNA sequencing that can be applied to any species. We validated Rerep-Seq by simulating DNA rereplication in yeast and human cells. Using Rerep-Seq, we demonstrate that rereplication induced in Saccharomyces cerevisiae by deregulated origin licensing is non-random and defined by broad domains that span multiple replication origins and topological boundaries.

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Punctuated Aneuploidization of the Budding Yeast Genome

Genetics ◽

10.1534/genetics.120.303536 ◽

2020 ◽

Vol 216 (1) ◽

pp. 43-50 ◽

Cited By ~ 2

Author(s):

Lydia R. Heasley ◽

Ruth A. Watson ◽

Juan Lucas Argueso

Keyword(s):

Saccharomyces Cerevisiae ◽

Tumor Cells ◽

Genomic Instability ◽

High Frequency ◽

Budding Yeast ◽

Cell Types ◽

Eukaryotic Cell ◽

Yeast Genome ◽

Single Chromosome ◽

Brewing Yeasts

Remarkably complex patterns of aneuploidy have been observed in the genomes of many eukaryotic cell types, ranging from brewing yeasts to tumor cells. Such aberrant karyotypes are generally thought to take shape progressively over many generations, but evidence also suggests that genomes may undergo faster modes of evolution. Here, we used diploid Saccharomyces cerevisiae cells to investigate the dynamics with which aneuploidies arise. We found that cells selected for the loss of a single chromosome often acquired additional unselected aneuploidies concomitantly. The degrees to which these genomes were altered fell along a spectrum, ranging from simple events affecting just a single chromosome, to systemic events involving many. The striking complexity of karyotypes arising from systemic events, combined with the high frequency at which we detected them, demonstrates that cells can rapidly achieve highly altered genomic configurations during temporally restricted episodes of genomic instability.

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Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae

eLife ◽

10.7554/elife.26884 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 19

Author(s):

Aurèle Piazza ◽

Xiaojie Cui ◽

Michael Adrian ◽

Frédéric Samazan ◽

Brahim Heddi ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Structure Function ◽

Genomic Instability ◽

Function Analysis ◽

Structural Features ◽

Detectable Effect ◽

Definition Of ◽

And Function

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4-forming sequences.

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Lack of superoxide dismutase in a rad51 mutant exacerbates genomic instability and oxidative stress-mediated cytotoxicity in Saccharomyces cerevisiae

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2018.09.015 ◽

2018 ◽

Vol 129 ◽

pp. 97-106 ◽

Cited By ~ 3

Author(s):

Ji Eun Choi ◽

Seo-Hee Heo ◽

Myung Ju Kim ◽

Woo-Hyun Chung

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Superoxide Dismutase ◽

Genomic Instability ◽

And Oxidative Stress

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Centromere Replication Timing Determines Different Forms of Genomic Instability in Saccharomyces cerevisiae Checkpoint Mutants During Replication Stress

Genetics ◽

10.1534/genetics.109.107508 ◽

2009 ◽

Vol 183 (4) ◽

pp. 1249-1260 ◽

Cited By ~ 30

Author(s):

Wenyi Feng ◽

Jeff Bachant ◽

David Collingwood ◽

M. K. Raghuraman ◽

Bonita J. Brewer

Keyword(s):

Saccharomyces Cerevisiae ◽

Genomic Instability ◽

Replication Timing ◽

Replication Stress

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A functional autophagy pathway is required for rapamycin-induced degradation of the Sgs1 helicase in Saccharomyces cerevisiae

Biochemistry and Cell Biology ◽

10.1139/bcb-2012-0084 ◽

2013 ◽

Vol 91 (3) ◽

pp. 123-130 ◽

Cited By ~ 1

Author(s):

Rim Marrakchi ◽

Chedly Chouchani ◽

Jeremie Poschmann ◽

Emil Andreev ◽

Mohamed Cherif ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Genomic Instability ◽

Biological Processes ◽

Yeast Saccharomyces Cerevisiae ◽

Rapid Degradation ◽

Yeast Strains ◽

Autophagy Pathway

In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin mimics starvation by inhibiting the kinase Tor1. We recently documented that this treatment triggers a rapid degradation of Sgs1, a helicase involved in several biological processes such as the prevention of genomic instability. Herein, we show that yeast strains deleted for genes ATG2, ATG9, and PEP4, encoding components of the autophagy pathway, prevent rapamycin-induced degradation of Sgs1. We propose that defects in the autophagy pathway prevent degradation of key proteins in the rapamycin response pathway and as a consequence cause resistance to the drug.

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Comparative genome analysis suggests characteristics of yeast inverted repeats that are important for transcriptional activity

Genome ◽

10.1139/g11-058 ◽

2011 ◽

Vol 54 (11) ◽

pp. 934-942 ◽

Cited By ~ 2

Author(s):

Emily L. Humphrey-Dixon ◽

Richard Sharp ◽

Michael Schuckers ◽

Robin Lock

Keyword(s):

Saccharomyces Cerevisiae ◽

Genomic Instability ◽

Genome Analysis ◽

Base Composition ◽

Transcriptional Activity ◽

Dna Structure ◽

Inverted Repeats ◽

Comparative Genome Analysis ◽

Comparative Genome

Inverted repeats are sequences of DNA that, when read in the 5′ to 3′ direction, have the same sequence on both strands (palindromic portion), with the exception of a small number of nucleotides in the exact center (nonpalindromic spacer). They have been implicated in various DNA-mediated processes including replication, transcription, and genomic instability. At least some of these sequences are capable of forming an alternative DNA structure, called a cruciform, that may be important for mediating these functions. We generated a list of inverted repeats in the Saccharomyces cerevisiae genome and determined which of them are conserved in three related yeasts. We have identified characterisitics of inverted repeats that make them more likely to be conserved than the surrounding DNA and characteristics, such as position and base composition, that make the genes they are associated with likely to be more actively transcribed. This is an important step in determining the functions of this group of genomic elements.

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Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae

DNA Repair ◽

10.1016/j.dnarep.2015.07.002 ◽

2015 ◽

Vol 35 ◽

pp. 1-12 ◽

Cited By ~ 20

Author(s):

Katherine A. Donigan ◽

Susana M. Cerritelli ◽

John P. McDonald ◽

Alexandra Vaisman ◽

Robert J. Crouch ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Genomic Instability ◽

Dna Polymerase

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Genomic Instability Is Associated with Natural Life Span Variation in Saccharomyces cerevisiae

PLoS ONE ◽

10.1371/journal.pone.0002670 ◽

2008 ◽

Vol 3 (7) ◽

pp. e2670 ◽

Cited By ~ 15

Author(s):

Hong Qin ◽

Meng Lu ◽

David S. Goldfarb

Keyword(s):

Saccharomyces Cerevisiae ◽

Life Span ◽

Genomic Instability ◽

Natural Life

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hpr1Δ Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.22.2.421-429.2002 ◽

2002 ◽

Vol 22 (2) ◽

pp. 421-429 ◽

Cited By ~ 41

Author(s):

Robert J. Merker ◽

Hannah L. Klein

Keyword(s):

Saccharomyces Cerevisiae ◽

Rna Polymerase ◽

Life Span ◽

Rna Polymerase Ii ◽

Genomic Instability ◽

Ribosomal Dna ◽

Dna Recombination ◽

Genetic Pathways ◽

Rdna Array ◽

Cell Life

ABSTRACT Multiple genetic pathways have been shown to regulate life span and aging in the yeast Saccharomyces cerevisiae. Here we show that loss of a component of the RNA polymerase II complex, Hpr1p, results in a decreased life span. Although hpr1Δ mutants have an increased rate of recombination within the ribosomal DNA (rDNA) array, this is not accompanied by an increase in extrachromosomal rDNA circles (ERCs). Analyses of mutants that affect replication of the rDNA array and suppressors that reverse the phenotypes of the hpr1Δ mutant show that the reduced life span is associated with increased genomic instability but not with increased ERC formation. The hpr1Δ mutant acts in a pathway distinct from previously described mutants that reduce life span.

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