scholarly journals Postreplication Repair Inhibits CAG · CTG Repeat Expansions in Saccharomyces cerevisiae

2006 ◽  
Vol 27 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Danielle L. Daee ◽  
Tony Mertz ◽  
Robert S. Lahue
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Trinucleotide Repeats ◽  
Dna Microsatellites ◽  
Dinucleotide Repeats ◽  
Replication Slippage ◽  
Postreplication Repair ◽  
Epistasis Analysis ◽  
Repeat Expansions ◽  
The Relationship ◽  
Ctg Repeat

ABSTRACTTrinucleotide repeats (TNRs) are unique DNA microsatellites that can expand to cause human disease. Recently, Srs2 was identified as a protein that inhibits TNR expansions inSaccharomyces cerevisiae. Here, we demonstrate that Srs2 inhibits CAG · CTG expansions in conjunction with the error-free branch of postreplication repair (PRR). Likesrs2mutants, expansions are elevated inrad18andrad5mutants, as well as the PRR-specific PCNA allelespol30-K164Randpol30-K127/164R. Epistasis analysis indicates that Srs2 acts upstream of these PRR proteins. Also, likesrs2mutants, thepol30-K127/164Rphenotype is specific for expansions, as this allele does not alter mutation rates at dinucleotide repeats, at nonrepeating sequences, or for CAG · CTG repeat contractions. Our results suggest that Srs2 action and PRR processing inhibit TNR expansions. We also investigated the relationship between PRR and Rad27 (Fen1), a well-established inhibitor of TNR expansions that acts at 5′ flaps. Our results indicate that PRR protects against expansions arising from the 3′ terminus, presumably replication slippage events. This work provides the first evidence that CAG · CTG expansions can occur by 3′ slippage, and our results help define PRR as a key cellular mechanism that protects against expansions.

scholarly journals Trinucleotide Repeats Are Clustered in Regulatory Genes in Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1053-1068 ◽  
Author(s):  
Elton T Young ◽  
James S Sloan ◽  
Kristen Van Riper
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Rapid Evolution ◽  
Trinucleotide Repeats ◽  
Cellular Regulation ◽  
Dinucleotide Repeats ◽  
C Terminus ◽  
Recent Origin ◽  
Structural Database ◽  
High Instability

Abstract The genome of Saccharomyces cerevisiae contains numerous unstable microsatellite sequences. Mononucleotide and dinucleotide repeats are rarely found in ORFs, and when present in an ORF are frequently located in an intron or at the C terminus of the protein, suggesting that their instability is deleterious to gene function. DNA trinucleotide repeats (TNRs) are found at a higher-than-expected frequency within ORFs, and the amino acids encoded by the TNRs represent a biased set. TNRs are rarely conserved between genes with related sequences, suggesting high instability or a recent origin. The genes in which TNRs are most frequently found are related to cellular regulation. The protein structural database is notably lacking in proteins containing amino acid tracts, suggesting that they are not located in structured regions of a protein but are rather located between domains. This conclusion is consistent with the location of amino acid tracts in two protein families. The preferred location of TNRs within the ORFs of genes related to cellular regulation together with their instability suggest that TNRs could have an important role in speciation. Specifically, TNRs could serve as hot spots for recombination leading to domain swapping, or mutation of TNRs could allow rapid evolution of new domains of protein structure.

scholarly journals Saccharomyces cerevisiae Srs2 DNA Helicase Selectively Blocks Expansions of Trinucleotide Repeats

2004 ◽  
Vol 24 (17) ◽  
pp. 7324-7330 ◽  
Author(s):  
Saumitri Bhattacharyya ◽  
Robert S. Lahue
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Recombination ◽  
Dna Helicase ◽  
Trinucleotide Repeats ◽  
Model Organisms ◽  
Helicase Activity ◽  
Dna Polymerase Delta ◽  
Dinucleotide Repeats ◽  
Cgg Repeats

ABSTRACT Trinucleotide repeats (TNRs) undergo frequent mutations in families afflicted with certain neurodegenerative disorders and in model organisms. TNR instability is modulated both by the repeat tract itself and by cellular proteins. Here we identified the Saccharomyces cerevisiae DNA helicase Srs2 as a potent and selective inhibitor of expansions. srs2 mutants had up to 40-fold increased expansion rates of CTG, CAG, and CGG repeats. The expansion phenotype was specific, as mutation rates at dinucleotide repeats, at unique sequences, or for TNR contractions in srs2 mutants were not altered. Srs2 is known to suppress inappropriate genetic recombination; however, the TNR expansion phenotype of srs2 mutants was largely independent of RAD51 and RAD52. Instead, Srs2 mainly functioned with DNA polymerase delta to block expansions. The helicase activity of Srs2 was important, because a point mutant lacking ATPase function was defective in blocking expansions. Purified Srs2 was substantially better than bacterial UvrD helicase at in vitro unwinding of a DNA substrate that mimicked a TNR hairpin. Disruption of the related helicase gene SGS1 did not lead to excess expansions, nor did wild-type SGS1 suppress the expansion phenotype of an srs2 strain. We conclude that Srs2 selectively blocks triplet repeat expansions through its helicase activity and primarily in conjunction with polymerase delta.

scholarly journals A yeast metabolome-based model for an ecotoxicological approach in the management of lignocellulosic ethanol stillage

2019 ◽  
Vol 6 (1) ◽  
pp. 180718 ◽  
Author(s):  
Luca Roscini ◽  
Lorenzo Favaro ◽  
Laura Corte ◽  
Lorenzo Cagnin ◽  
Claudia Colabella ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Saccharomyces Cerevisiae ◽  
Predictive Model ◽  
Lignocellulosic Ethanol ◽  
Bioethanol Production ◽  
Inhibitor Concentration ◽  
Promising Tool ◽  
Different Types ◽  
The Relationship ◽  
Ecotoxicological Bioassay

Lignocellulosic bioethanol production results in huge amounts of stillage, a potentially polluting by-product. Stillage, rich in heavy metals and, mainly, inhibitors, requires specific toxicity studies to be adequately managed. To this purpose, we applied an FTIR ecotoxicological bioassay to evaluate the toxicity of lignocellulosic stillage. Two weak acids and furans, most frequently found in lignocellulosic stillage, have been tested in different mixtures against three Saccharomyces cerevisiae strains. The metabolomic reaction of the test microbes and the mortality induced at various levels of inhibitor concentration showed that the strains are representative of three different types of response. Furthermore, the relationship between concentrations and FTIR synthetic stress indexes has been studied, with the aim of defining a model able to predict the concentrations of inhibitors in stillage, resulting in an optimized predictive model for all the strains. This approach represents a promising tool to support the ecotoxicological management of lignocellulosic stillage.

An investigation into the relationship between anti-Helicobacter pylori and anti-Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and Crohn disease

2014 ◽  
Vol 35 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Igor Kunze Rodrigues ◽  
Michele Andrigueti ◽  
Ione Dilma de Oliveira Gil ◽  
Leonardo de Lucca Schiavon ◽  
Kenia Rodrigues de Andrade ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Helicobacter Pylori ◽  
Crohn Disease ◽  
Axial Spondyloarthritis ◽  
The Relationship

scholarly journals A Mep2-dependent Transcriptional Profile Links Permease Function to Gene Expression during Pseudohyphal Growth in Saccharomyces cerevisiae

2008 ◽  
Vol 19 (7) ◽  
pp. 3028-3039 ◽  
Author(s):  
Julian C. Rutherford ◽  
Gordon Chua ◽  
Timothy Hughes ◽  
Maria E. Cardenas ◽  
Joseph Heitman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Map Kinase ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Transcriptional Profile ◽  
Regulatory Function ◽  
Pseudohyphal Growth ◽  
Epistasis Analysis ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a regulatory function, supporting models in which Mep2 acts as a sensor of ammonium availability. Potentially similar ammonium permease-dependent regulatory cascades operate in other fungi, and they may also function in animals via the homologous Rh proteins; however, little is known about the molecular mechanisms that mediate ammonium sensing. We show that Mep2 is localized to the cell surface during pseudohyphal growth, and it is required for both filamentous and invasive growth. Analysis of site-directed Mep2 mutants in residues lining the ammonia-conducting channel reveal separation of function alleles (transport and signaling defective; transport-proficient/signaling defective), indicating transport is necessary but not sufficient to sense ammonia. Furthermore, Mep2 overexpression enhances differentiation under normally repressive conditions and induces a transcriptional profile that is consistent with activation of the mitogen-activated protein (MAP) kinase pathway. This finding is supported by epistasis analysis establishing that the known role of the MAP kinase pathway in pseudohyphal growth is linked to Mep2 function. Together, these data strengthen the model that Mep2-like proteins are nutrient sensing transceptors that govern cellular differentiation.

Examination of the relationship between parameters to determine electropermeability of Saccharomyces cerevisiae

1999 ◽  
Vol 48 (2) ◽  
pp. 485-488 ◽  
Author(s):  
Masafumi Muraji ◽  
Hiroaki Taniguchi ◽  
Wataru Tatebe ◽  
Hermann Berg
Keyword(s):  
Saccharomyces Cerevisiae ◽  
The Relationship

scholarly journals The Saccharomyces cerevisiae Rad6 Postreplication Repair and Siz1/Srs2 Homologous Recombination-Inhibiting Pathways Process DNA Damage That Arises in asf1 Mutants

2009 ◽  
Vol 29 (19) ◽  
pp. 5226-5237 ◽  
Author(s):  
Ellen S. Kats ◽  
Jorrit M. Enserink ◽  
Sandra Martinez ◽  
Richard D. Kolodner
Keyword(s):  
Homologous Recombination ◽  
Genome Stability ◽  
Chromosomal Rearrangements ◽  
Nuclear Antigen ◽  
Recombination Suppression ◽  
Postreplication Repair ◽  
Gross Chromosomal Rearrangements ◽  
Translesion Bypass ◽  
The Relationship ◽  
Proliferating Cell

ABSTRACT The Asf1 and Rad6 pathways have been implicated in a number of common processes such as suppression of gross chromosomal rearrangements (GCRs), DNA repair, modification of chromatin, and proper checkpoint functions. We examined the relationship between Asf1 and different gene products implicated in postreplication repair (PRR) pathways in the suppression of GCRs, checkpoint function, sensitivity to hydroxyurea (HU) and methyl methanesulfonate (MMS), and ubiquitination of proliferating cell nuclear antigen (PCNA). We found that defects in Rad6 PRR pathway and Siz1/Srs2 homologous recombination suppression (HRS) pathway genes suppressed the increased GCR rates seen in asf1 mutants, which was independent of translesion bypass polymerases but showed an increased dependency on Dun1. Combining an asf1 deletion with different PRR mutations resulted in a synergistic increase in sensitivity to chronic HU and MMS treatment; however, these double mutants were not checkpoint defective, since they were capable of recovering from acute treatment with HU. Interestingly, we found that Asf1 and Rad6 cooperate in ubiquitination of PCNA, indicating that Rad6 and Asf1 function in parallel pathways that ubiquitinate PCNA. Our results show that ASF1 probably contributes to the maintenance of genome stability through multiple mechanisms, some of which involve the PRR and HRS pathways.

Sign in / Sign up

Export Citation Format

Share Document