Genomes and Genes
Gene Symbol: YKU70
Description: ATP-dependent DNA helicase YKU70
Alias: HDF1, NES24, ATP-dependent DNA helicase YKU70
Species: Saccharomyces cerevisiae S288c
- Polotnianka R, Li J, Lustig A. The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr Biol. 1998;8:831-4 pubmed..Furthermore, mutations in HDF1 or HDF2 rapidly reduce telomeric poly (TG1-3) tract size [1-3], hinting also at a possible telomeric function of Ku...
- Wu T, Chiang Y, Lin Y, Tsai C, Yu T, Sung M, et al. Sequential loading of Saccharomyces cerevisiae Ku and Cdc13p to telomeres. J Biol Chem. 2009;284:12801-8 pubmed publisher..Our results also offer a mechanism that the binding of Cdc13p to telomeres might prevent Yku from initiating DNA double-stranded break repair pathway on telomeres. ..
- Stellwagen A, Haimberger Z, Veatch J, Gottschling D. Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes Dev. 2003;17:2384-95 pubmed..Thus, the interaction between Ku and TLC1 RNA enables telomerase to act at both broken and normal chromosome ends. ..
- Marvin M, Becker M, Noel P, Hardy S, Bertuch A, Louis E. The association of yKu with subtelomeric core X sequences prevents recombination involving telomeric sequences. Genetics. 2009;183:453-67, 1SI-13SI pubmed publisher..We believe our findings support our hypothesis that yKu and core X play a pivotal role in maintaining genome stability through nuclear architecture by mediating a defensive fold-back structure at yeast chromosome ends. ..
- Vega L, Phillips J, Thornton B, Benanti J, Onigbanjo M, Toczyski D, et al. Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase. PLoS Genet. 2007;3:e105 pubmed..These data suggest that wild-type levels of telomere-bound telomerase are critical for the viability of strains whose telomeres are already susceptible to degradation. ..
- Zhao X, Blobel G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A. 2005;102:4777-82 pubmed..The substrates for this SUMO ligase include a subunit of the octameric complex, Smc5, and the DNA repair protein Yku70. We further show that the abolition of the SUMO E3 activity of Mms21 leads to such disparate phenotypes as DNA ..
- Shim E, Chung W, Nicolette M, Zhang Y, Davis M, Zhu Z, et al. Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks. EMBO J. 2010;29:3370-80 pubmed publisher..However, Mre11 nuclease activity is essential for resection in the absence of extensive resection enzymes. The results provide new insights into how MRX catalyses end resection and recombination initiation. ..
- Pellicioli A, Lee S, Lucca C, Foiani M, Haber J. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol Cell. 2001;7:293-300 pubmed..We conclude that activation of the checkpoint kinases in response to a single DNA break is cell cycle regulated and that adaptation is an active process by which these kinases are inactivated. ..
- Marvin M, Griffin C, Eyre D, Barton D, Louis E. In Saccharomyces cerevisiae, yKu and subtelomeric core X sequences repress homologous recombination near telomeres as part of the same pathway. Genetics. 2009;183:441-51, 1SI-12SI pubmed publisher..Furthermore, core X bestowed this protection as part of the same pathway as yKu. Our findings implicate a role for both yKu and core X in stabilizing the genome against recombination events involving telomeric sequences. ..
- Lopez C, Ribes Zamora A, Indiviglio S, Williams C, Haricharan S, Bertuch A. Ku must load directly onto the chromosome end in order to mediate its telomeric functions. PLoS Genet. 2011;7:e1002233 pubmed publisher..The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance. ..
- Myung K, Chen C, Kolodner R. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature. 2001;411:1073-6 pubmed..Mutations that inactivate these pathways cause high rates of GCRs and show synergistic interactions, indicating that the pathways that suppress GCRs all compete for the same DNA substrates. ..
- Teo S, Jackson S. Telomerase subunit overexpression suppresses telomere-specific checkpoint activation in the yeast yku80 mutant. EMBO Rep. 2001;2:197-202 pubmed..In Saccharomyces cerevisiae, deletion of YKU70 or YKU80 results in an inability to grow at 37 degrees C...
- Martin S, Laroche T, Suka N, Grunstein M, Gasser S. Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell. 1999;97:621-33 pubmed..Consistently, yKu- or SIR-deficient strains are hypersensitive to DNA-damaging agents. The release of yKu from telomeric chromatin may allow efficient scanning of the genome for DNA strand breaks. ..
- Vandre C, Kamakaka R, Rivier D. The DNA end-binding protein Ku regulates silencing at the internal HML and HMR loci in Saccharomyces cerevisiae. Genetics. 2008;180:1407-18 pubmed publisher..Here, we tested whether Ku contributes to silencing at HML or HMR. Mutant analysis revealed that yKu70 and Sir1 act collectively to silence the mating-type genes at HML and HMR...
- Patterson E, Fox C. The Ku complex in silencing the cryptic mating-type loci of Saccharomyces cerevisiae. Genetics. 2008;180:771-83 pubmed publisher..Additional ChIP experiments provided evidence that Ku functioned directly at the HM loci. Thus Ku and Sir1 had overlapping roles in silencing the HM loci. ..
- Tsolou A, Lydall D. Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1. DNA Repair (Amst). 2007;6:1607-17 pubmed..Our observations show that Mrc1, a core component of the replication fork, plays an important role in telomere capping, protecting from nucleases and checkpoint pathways. ..
- Boulton S, Jackson S. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO J. 1996;15:5093-103 pubmed..However, yku70 mutations enhance the radiosensitivity of rad52 strains, which are deficient in homologous recombination...
- Lee S, Moore J, Holmes A, Umezu K, Kolodner R, Haber J. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell. 1998;94:399-409 pubmed..b>hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint...
- Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, et al. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell. 2006;124:1155-68 pubmed..Our results therefore indicate that the KEOPS complex promotes both telomere uncapping and telomere elongation. ..
- Tong X, Li Q, Duan Y, Liu N, Zhang M, Zhou J. Est1 protects telomeres and inhibits subtelomeric y'-element recombination. Mol Cell Biol. 2011;31:1263-74 pubmed publisher..Our results demonstrate that one major functional role that Est1 brings to the telomerase complex is the capping or protection of telomeres. ..
- Corda Y, Lee S, Guillot S, Walther A, Sollier J, Arbel Eden A, et al. Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by depleting the ribonucleotide reductase inhibitor Sml1 through a pathway controlled by Tel1 kinase and the Mre11 complex. Mol Cell Biol. 2005;25:10652-64 pubmed..We report that deletion of YKU70 or YKU80 suppresses mec1Delta, but not rad53Delta, lethality...
- Grandin N, Charbonneau M. Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Mol Genet Genomics. 2007;277:685-99 pubmed..Here, we report that in the absence of Mrc1, a component of the replication forks, telomeres of cdc13 or yku70 mutants exhibited increased degradation, while telomerase-negative cells displayed accelerated senescence...
- Boulton S, Jackson S. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 1998;17:1819-28 pubmed..These data provide important insights into DNA DSB repair and the linkage of this process to telomere length homeostasis and transcriptional silencing. ..
- Bonetti D, Clerici M, Manfrini N, Lucchini G, Longhese M. The MRX complex plays multiple functions in resection of Yku- and Rif2-protected DNA ends. PLoS ONE. 2010;5:e14142 pubmed publisher..Thus, resection of DNA ends that are protected by Yku and Rif2 involves multiple functions of the MRX complex that do not necessarily require its nuclease activity. ..
- Krishna S, Wagener B, Liu H, Lo Y, Sterk R, Petrini J, et al. Mre11 and Ku regulation of double-strand break repair by gene conversion and break-induced replication. DNA Repair (Amst). 2007;6:797-808 pubmed..BIR is also elevated in rad51 mutants, but yku70Delta did not suppress BIR in a rad51 background. These results indicate that Mre11 functions in Rad51-independent BIR, and that Ku functions in Rad51-dependent BIR. ..
- Lee K, Lee S. Saccharomyces cerevisiae Sae2- and Tel1-dependent single-strand DNA formation at DNA break promotes microhomology-mediated end joining. Genetics. 2007;176:2003-14 pubmed..Sae2 and Tel1 promote MMEJ but inhibit NHEJ, likely by regulating Mre11-dependent ssDNA accumulation at DNA break. Our data support the role of Sae2 and Tel1 in MMEJ and genome integrity. ..
- Vodenicharov M, Laterreur N, Wellinger R. Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J. 2010;29:3007-19 pubmed publisher..However, Yku and Rap1 become crucially important for this function in these cells. After inactivation of Yku70 in G1-arrested cells, moderate but significant telomere degradation occurs...
- Blankley R, Lydall D. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci. 2004;117:601-8 pubmed..This work extends data showing that separable domains within the Rad9 adaptor protein allow it to activate two distinct kinase signalling pathways independently of each other. ..
- Clerici M, Mantiero D, Guerini I, Lucchini G, Longhese M. The Yku70-Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle. EMBO Rep. 2008;9:810-8 pubmed publisher..Here, we show that a lack of any of the NHEJ proteins Yku (Yku70-Yku80), Lif1 or DNA ligase IV (Dnl4) increases 5' DSB end degradation in G1 phase, with ykuDelta cells showing the ..
- Evans S, Lundblad V. The Est1 subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance. Genetics. 2002;162:1101-15 pubmed..The isolation of mutations that perturb separate functions of Est1 demonstrates that a telomerase holoenzyme subunit can contribute multiple regulatory roles to telomere length maintenance. ..
- Foster S, Balestrini A, Petrini J. Functional interplay of the Mre11 nuclease and Ku in the response to replication-associated DNA damage. Mol Cell Biol. 2011;31:4379-89 pubmed publisher..We have previously shown that in Saccharomyces cerevisiae, Ku70 (yKu70) deficiency reduces the ionizing radiation sensitivity of mre11? mutants...
- Nugent C, Bosco G, Ross L, Evans S, Salinger A, Moore J, et al. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol. 1998;8:657-60 pubmed..Ku, Cdc13 and telomerase define three epistasis groups required in parallel for telomere maintenance. ..
- Tsukamoto Y, Kato J, Ikeda H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature. 1997;388:900-3 pubmed..One of the factors involved in the end-joining process is Hdf1, a yeast homologue of Ku protein...
- Zhang W, Durocher D. De novo telomere formation is suppressed by the Mec1-dependent inhibition of Cdc13 accumulation at DNA breaks. Genes Dev. 2010;24:502-15 pubmed publisher..These studies therefore identify a mechanism by which the ATR family of kinases enforces genome integrity, and a process that underscores the contribution of Cdc13 to the fate of DNA ends. ..
- Ribes Zamora A, Mihalek I, Lichtarge O, Bertuch A. Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nat Struct Mol Biol. 2007;14:301-7 pubmed..We propose a 'two-face' model for Ku and that divergent evolution of these faces allowed Ku's dual role in NHEJ and telomere maintenance. ..
- Banerjee S, Smith S, Myung K. Suppression of gross chromosomal rearrangements by yKu70-yKu80 heterodimer through DNA damage checkpoints. Proc Natl Acad Sci U S A. 2006;103:1816-21 pubmed..To understand the mechanism of Ku as a genome gatekeeper, we overexpressed the yKu70-yKu80 heterodimer and monitored the formation of GCRs...
- Grandin N, Damon C, Charbonneau M. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol Cell Biol. 2000;20:8397-408 pubmed..depended on telomerase (Est2/TLC1) and Est1, a direct regulator of telomerase, but also on the yeast Ku proteins, yKu70/Hdf1 and yKu80/Hdf2, that have been previously implicated in DNA repair and telomere maintenance...
- Driller L, Wellinger R, Larrivee M, Kremmer E, Jaklin S, Feldmann H. A short C-terminal domain of Yku70p is essential for telomere maintenance. J Biol Chem. 2000;275:24921-7 pubmed..the role of the Yku70p subunit in these two different pathways, we generated C-terminal deletions of the Yku70 protein and examined their ability to complement the phenotypes of a yku70(-) strain...
- Bonetti D, Clerici M, Anbalagan S, Martina M, Lucchini G, Longhese M. Shelterin-like proteins and Yku inhibit nucleolytic processing of Saccharomyces cerevisiae telomeres. PLoS Genet. 2010;6:e1000966 pubmed publisher..Thus, chromosome end degradation is controlled by telomeric proteins that specifically inhibit the action of different nucleases. ..
- Ui A, Seki M, Ogiwara H, Onodera R, Fukushige S, Onoda F, et al. The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination. DNA Repair (Amst). 2005;4:191-201 pubmed
- Dzierzbicki P, Kaniak Golik A, Malc E, Mieczkowski P, Ciesla Z. The generation of oxidative stress-induced rearrangements in Saccharomyces cerevisiae mtDNA is dependent on the Nuc1 (EndoG/ExoG) nuclease and is enhanced by inactivation of the MRX complex. Mutat Res. 2012;740:21-33 pubmed publisher..This result indicates that the nuclease plays an important role in processing of oxidative stress-induced lesions in the mitochondrial genome. ..
- Grandin N, Corset L, Charbonneau M. Genetic and physical interactions between Tel2 and the Med15 Mediator subunit in Saccharomyces cerevisiae. PLoS ONE. 2012;7:e30451 pubmed publisher..Altogether, the present data suggest the existence of a novel role for Tel2, namely in transcription, possibly in cooperation with Rvb2 and involving the existence of physical interactions with the Med15/Gal11 Mediator subunit. ..
- Iwasaki D, Hayashihara K, Shima H, Higashide M, Terasawa M, Gasser S, et al. The MRX Complex Ensures NHEJ Fidelity through Multiple Pathways Including Xrs2-FHA-Dependent Tel1 Activation. PLoS Genet. 2016;12:e1005942 pubmed publisher..Thus, the Xrs2 FHA domain and Tel1 kinase work in a coordinated manner to maintain DSB repair fidelity. ..
- Ruiz Gómez M. Telomere instability caused by subtelomeric Y' amplification and rearrangements in Saccharomyces cerevisiae (ku70 tel1 and ku70 rad50) double mutants. Indian J Exp Biol. 2011;49:324-31 pubmedTelomeres solve the end-replication problem. Previous results suggested a relation between Yku70/80 and proteins Tell and Rad50 in telomere stabilization...
- Shim E, Ma J, Oum J, Yanez Y, Lee S. The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA double-strand breaks. Mol Cell Biol. 2005;25:3934-44 pubmed..Recruitment of RSC to a DSB depends on Mre11, Rsc30, and yKu70 proteins. Rsc1p and Rsc2p, two other RSC subunits, physically interact with yKu80p and Mre11p...
- Yamana Y, Maeda T, Ohba H, Usui T, Ogawa H, Kusano K. Regulation of homologous integration in yeast by the DNA repair proteins Ku70 and RecQ. Mol Genet Genomics. 2005;273:167-76 pubmed..We present evidence for a genetic interaction between SGS1 and YKU70, which encodes the S. cerevisiae homologue of the human DNA helicase Ku70...
- Norden C, Mendoza M, Dobbelaere J, Kotwaliwale C, Biggins S, Barral Y. The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage. Cell. 2006;125:85-98 pubmed..We propose that NoCut monitors clearance of chromatin from the midzone to ensure that cytokinesis completes only after all chromosomes have migrated to the poles. ..
- Soustelle C, Vernis L, Fréon K, Reynaud Angelin A, Chanet R, Fabre F, et al. A new Saccharomyces cerevisiae strain with a mutant Smt3-deconjugating Ulp1 protein is affected in DNA replication and requires Srs2 and homologous recombination for its viability. Mol Cell Biol. 2004;24:5130-43 pubmed..These structures are believed to generate different recombination intermediates. Some of them are fixed by recombination, and others require Srs2 to be reversed and fixed by an alternate pathway. ..
- Yu L, Volkert M. Differential requirement for SUB1 in chromosomal and plasmid double-strand DNA break repair. PLoS ONE. 2013;8:e58015 pubmed publisher..Possible roles for Sub1 proteins in NHEJ of plasmid DNA are discussed. ..
- Matsuzaki K, Terasawa M, Iwasaki D, Higashide M, Shinohara M. Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection. Genes Cells. 2012;17:473-93 pubmed publisher..CDK-dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways. ..
- Simoneau A, Ricard Ã, Weber S, Hammond Martel I, Wong L, Sellam A, et al. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress. Nucleic Acids Res. 2016;44:2706-26 pubmed publisher..Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. ..
- Ponnusamy S, Alderson N, Hama H, Bielawski J, Jiang J, Bhandari R, et al. Regulation of telomere length by fatty acid elongase 3 in yeast. Involvement of inositol phosphate metabolism and Ku70/80 function. J Biol Chem. 2008;283:27514-24 pubmed publisher..to determine downstream mechanisms, epistasis experiments were performed, and data indicated that ELO3 and YKU70/80 share a common pathway for the regulation of telomere length...
- Hass E, Zappulla D. The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae. elife. 2015;4: pubmed publisher..These findings suggest that Sir4 is the telomere-bound target of Ku-mediated telomerase recruitment and provide one mechanism for how the Sir4-competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast. ..
- Westmoreland J, Resnick M. Coincident resection at both ends of random, ?-induced double-strand breaks requires MRX (MRN), Sae2 (Ctp1), and Mre11-nuclease. PLoS Genet. 2013;9:e1003420 pubmed publisher..These approaches apply to resection at other DSBs. Given evolutionary conservation, the observations are relevant to DNA repair in human cells. ..
- Grund S, Fischer T, Cabal G, Antúnez O, Pérez Ortín J, Hurt E. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression. J Cell Biol. 2008;182:897-910 pubmed publisher..Our data show that the inner nuclear membrane protein Src1 functions at the interface between subtelomeric gene expression and TREX-dependent messenger RNA export through the nuclear pore complexes. ..
- Porter S, Greenwell P, Ritchie K, Petes T. The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 1996;24:582-5 pubmed..and Jaspers, N.G.J. (1994) Curr. Biol., 4, 1149- 1151]. A yeast gene (HDF1) encoding a putative homologue of the 70 kDa subunit of Ku has recently been identified [Feldmann, H...
- Downs J, Kosmidou E, Morgan A, Jackson S. Suppression of homologous recombination by the Saccharomyces cerevisiae linker histone. Mol Cell. 2003;11:1685-92 pubmed..Finally, we show that Hho1p is inhibitory to the recombination-dependent mechanism of telomere maintenance. The role of linker histones in genome stability, aging, and tumorigenesis is discussed. ..
- Srividya I, Tirupataiah S, Mishra K. Yeast transcription termination factor Rtt103 functions in DNA damage response. PLoS ONE. 2012;7:e31288 pubmed publisherb>YKu70/YKu80 is a heterodimer that is essential for repair of DNA double strand breaks through non-homologous end joining pathway in the yeast Saccharomyces cerevisiae...
- Smith S, Banerjee S, Rilo R, Myung K. Dynamic regulation of single-stranded telomeres in Saccharomyces cerevisiae. Genetics. 2008;178:693-701 pubmed publisher..Therefore, the yKu70-80 heterodimer and telomerase maintain telomere size, and the helicase activity of Pif1 likely also helps to ..
- Titos I, Ivanova T, Mendoza M. Chromosome length and perinuclear attachment constrain resolution of DNA intertwines. J Cell Biol. 2014;206:719-33 pubmed publisher..We propose that topological constraints imposed by chromosome length and perinuclear attachment determine the amount of SCI that topo II and dynamic microtubules resolve during anaphase. ..
- Traven A, Lo T, Pike B, Friesen H, Guzzo J, Andrews B, et al. Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae. Yeast. 2010;27:41-52 pubmed publisher..Overall, the results indicate that Mdt1 has partially separable functions in both cell wall and genome integrity pathways. ..
- Pasupala N, Easwaran S, Hannan A, Shore D, Mishra K. The SUMO E3 ligase Siz2 exerts a locus-dependent effect on gene silencing in Saccharomyces cerevisiae. Eukaryot Cell. 2012;11:452-62 pubmed publisher..These data support the idea that sumoylation of specific substrates at the nuclear periphery regulates the availability of Sir2 protein at telomeres. ..
- Mániková D, Vlasáková D, Loduhová J, Letavayová L, Vigasová D, Krascsenitsová E, et al. Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae. Mutagenesis. 2010;25:155-62 pubmed publisher