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Addinall SG, et al.  (2011) Quantitative Fitness Analysis Shows That NMD Proteins and Many Other Protein Complexes Suppress or Enhance Distinct Telomere Cap Defects. PLoS Genet 7(4):e1001362

Abstract: To better understand telomere biology in budding yeast, we have performed systematic suppressor/enhancer analyses on yeast strains containing a point mutation in the essential telomere capping gene CDC13 (cdc13-1) or containing a null mutation in the DNA damage response and telomere capping gene YKU70 (yku70Delta). We performed Quantitative Fitness Analysis (QFA) on thousands of yeast strains containing mutations affecting telomere-capping proteins in combination with a library of systematic gene deletion mutations. To perform QFA, we typically inoculate 384 separate cultures onto solid agar plates and monitor growth of each culture by photography over time. The data are fitted to a logistic population growth model; and growth parameters, such as maximum growth rate and maximum doubling potential, are deduced. QFA reveals that as many as 5% of systematic gene deletions, affecting numerous functional classes, strongly interact with telomere capping defects. We show that, while Cdc13 and Yku70 perform complementary roles in telomere capping, their genetic interaction profiles differ significantly. At least 19 different classes of functionally or physically related proteins can be identified as interacting with cdc13-1, yku70Delta, or both. Each specific genetic interaction informs the roles of individual gene products in telomere biology. One striking example is with genes of the nonsense-mediated RNA decay (NMD) pathway which, when disabled, suppress the conditional cdc13-1 mutation but enhance the null yku70Delta mutation. We show that the suppressing/enhancing role of the NMD pathway at uncapped telomeres is mediated through the levels of Stn1, an essential telomere capping protein, which interacts with Cdc13 and recruitment of telomerase to telomeres. We show that increased Stn1 levels affect growth of cells with telomere capping defects due to cdc13-1 and yku70Delta. QFA is a sensitive, high-throughput method that will also be useful to understand other aspects of microbial cell biology.

Status: Published Type: Journal Article PubMed ID: 21490951

Topics addressed in this paper

Number of different genes curated to this paper: 86

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ARP6 CDC13 CHD1 CHL1 CKA1 CKA2 CKB1 CKB2 CTF18 CTF4
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Topics Genes linked to topics (#11 - 20 )
CTF8 DCC1 DDC1 DPH1 DPH2 DPH5 EBS1 ELG1 ELP2 ELP3
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Topics Genes linked to topics (#21 - 30 )
ELP4 ELP6 EST1 EST2 EST3 EXO1 FET3 FTR1 IKI3 JJJ3
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Topics Genes linked to topics (#31 - 40 )
KAR3 MAK10 MAK3 MAK31 MLP1 MLP2 MRC1 MRE11 NAM7 NMD2
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Alias blue ball blue ball
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Topics Genes linked to topics (#41 - 50 )
OCA1 OCA2 OCA4 OCA5 PEP8 PPH3 RAD17 RAD24 RAD50 RAD51
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Topics Genes linked to topics (#51 - 60 )
RAD52 RAD54 RAD55 RAD57 RAD61 RIF1 RIF2 RRD1 SGF11 SGF73
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Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#61 - 70 )
SIW14 SKI2 SKI7 SKI8 SPE1 SPE2 SPE3 SPT3 SPT8 STN1
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Topics Genes linked to topics (#71 - 80 )
SWC3 SWR1 TEL1 TEN1 UBP8 UPF3 VPS17 VPS29 VPS35 VPS5
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Topics Genes linked to topics (#81 - 86 )
VPS71 VPS72 XRS2 YAF9 YKU70 YKU80
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Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball
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