A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection

Greenall, Amanda; Lei, Guiyuan; Swan, Daniel; James, Katherine; Wang, Liming; Peters, Heiko; Wipat, Anil; Wilkinson, Darren J.; Lydall, David

doi:10.1186/gb-2008-9-10-r146

Cited by 20 publications

(17 citation statements)

References 57 publications

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“…4J)(8). Previous studies showed that defects in kyurenine biosynthesis suppressed cdc13-1 TS mutants, suggesting that elevated NAD+ levels inhibit telomere capping (23). Thus, the global genetic interaction network traced novel functional connections whereby defects in MTC pathway-dependent protein trafficking alter aromatic amino acid homeostasis, which appears to modulate steady state levels of kyurenine biosynthetic pathway metabolites, linking cell polarity to telomere capping through altered NAD+ levels.…”

Section: Predicting Novel Gene Functionmentioning

confidence: 99%

A global genetic interaction network maps a wiring diagram of cellular function

Costanzo

VanderSluis

Koch

et al. 2016

Science

1,107

105

1,607

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We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.

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Section: Predicting Novel Gene Functionmentioning

confidence: 99%

A global genetic interaction network maps a wiring diagram of cellular function

Costanzo

VanderSluis

Koch

et al. 2016

Science

1,107

105

1,607

View full text Add to dashboard Cite

show abstract

“…Additionally, independent genome-wide screens for deletion mutants showing genetic interactions with the cdc13-1 mutation had been performed [30], [31]. Ranking the screened genes on the basis of their temporal gene expression revealed that the genes with the highest DCeN values were enriched with genetic interactions with cdc13-1 (permutation test, most significant p = 0.014; Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Time-Resolved Gene Expression Measurements across Individuals

Elo

Schwikowski

2013

PLoS ONE

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Genetic and environmental determinants of altered cellular function, disease state, and drug response are increasingly studied using time-resolved transcriptomic profiles. While it is widely acknowledged that the rate of biological processes may vary between individuals, data analysis approaches that go beyond evaluating differential expression of single genes have so far not taken this variability into account. To this end, we introduce here a robust multi-gene data analysis approach and evaluate it in a biomarker discovery scenario across four publicly available datasets. In our evaluation, existing methods perform surprisingly poorly on time-resolved data; only the approach taking the variability into account yields reproducible and biologically plausible results. Our results indicate the need to capture gene expression between potentially heterogeneous individuals at multiple time points, and highlight the importance of robust data analysis in the presence of heterogeneous gene expression responses.

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“…cruzi , suggesting that GAPDH can sense the redox state, which subsequently controls whether it associates with telomeric DNA. The involvement of NAD + in a chromosomal end protection mechanism was also observed in yeast [ 35 ]. Our data also suggests that treatment with exogenous NAD + trigger translocation of GAPDH to nucleolus.…”

Section: Discussionmentioning

confidence: 96%

Glyceraldehyde 3-Phosphate Dehydrogenase-Telomere Association Correlates with Redox Status in Trypanosoma cruzi

et al. 2015

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Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a classical metabolic enzyme involved in energy production and plays a role in additional nuclear functions, including transcriptional control, recognition of misincorporated nucleotides in DNA and maintenance of telomere structure. Here, we show that the recombinant protein T. cruzi GAPDH (rTcGAPDH) binds single-stranded telomeric DNA. We demonstrate that the binding of GAPDH to telomeric DNA correlates with the balance between oxidized and reduced forms of nicotinamide adenine dinucleotides (NAD+/NADH). We observed that GAPDH-telomere association and NAD+/NADH balance changed throughout the T. cruzi life cycle. For example, in replicative epimastigote forms of T. cruzi, which show similar intracellular concentrations of NAD+ and NADH, GAPDH binds to telomeric DNA in vivo and this binding activity is inhibited by exogenous NAD+. In contrast, in the T. cruzi non-proliferative trypomastigote forms, which show higher NAD+ concentration, GAPDH was absent from telomeres. In addition, NAD+ abolishes physical interaction between recombinant GAPDH and synthetic telomere oligonucleotide in a cell free system, mimicking exogenous NAD+ that reduces GAPDH-telomere interaction in vivo. We propose that the balance in the NAD+/NADH ratio during T. cruzi life cycle homeostatically regulates GAPDH telomere association, suggesting that in trypanosomes redox status locally modulates GAPDH association with telomeric DNA.

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A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection

Abstract: NAD+ metabolism may be linked to telomere end protection in yeast.

Cited by 20 publications

References 57 publications

A global genetic interaction network maps a wiring diagram of cellular function

A global genetic interaction network maps a wiring diagram of cellular function

Analysis of Time-Resolved Gene Expression Measurements across Individuals

Glyceraldehyde 3-Phosphate Dehydrogenase-Telomere Association Correlates with Redox Status in Trypanosoma cruzi

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