Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends.

Abstract:

:The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. Our results using a tagged Ku complex, or a chromosome end capturing method, in budding yeast show that yKu association with telomeres can occur at sites distant from the physical end, on sub-telomeric elements, as well as on interstitial telomeric repeats. Consistent with previous studies, our results also show that yKu associates with telomeres in two distinct and independent ways: either via protein-protein interactions between Yku80 and Sir4 or via direct DNA binding. Importantly, yKu associates with the new sites reported here via both modes. Therefore, in sir4Δ cells, telomere bound yKu molecules must have loaded from a DNA-end near the transition of non-telomeric to telomeric repeat sequences. Such ends may have been one sided DNA breaks that occur as a consequence of stalled replication forks on or near telomeric repeat DNA. Altogether, the results predict a new model for yKu function at telomeres that involves yKu binding at one-sided DNA breaks caused by replication stalling. On telomere proximal chromatin, this binding is not followed by initiation of non-homologous end-joining, but rather by break-induced replication or repeat elongation by telomerase. After repair, the yKu-distal portion of telomeres is bound by Rap1, which in turn reduces the potential for yKu to mediate NHEJ. These results thus propose a solution to a long-standing conundrum, namely how to accommodate the apparently conflicting functions of Ku on telomeres.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Larcher MV,Pasquier E,MacDonald RS,Wellinger RJ

doi

10.1371/journal.pgen.1006479

subject

Has Abstract

pub_date

2016-12-08 00:00:00

pages

e1006479

issue

12

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-16-01086

journal_volume

12

pub_type

杂志文章
  • Correction: Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1006788.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1006893

    authors: Sharma V,Pandey AK,Kumar A,Misra S,Gupta HPK,Gupta S,Singh A,Buehner NA,Ravi Ram K

    更新日期:2017-07-12 00:00:00

  • Glucocorticoid receptor-dependent gene regulatory networks.

    abstract::While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expressi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0010016

    authors: Phuc Le P,Friedman JR,Schug J,Brestelli JE,Parker JB,Bochkis IM,Kaestner KH

    更新日期:2005-08-01 00:00:00

  • Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

    abstract::Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease ph...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000399

    authors: Gidalevitz T,Krupinski T,Garcia S,Morimoto RI

    更新日期:2009-03-01 00:00:00

  • Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    abstract::Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and ver...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005402

    authors: Chance RK,Bashaw GJ

    更新日期:2015-09-03 00:00:00

  • A cis-acting diversification activator both necessary and sufficient for AID-mediated hypermutation.

    abstract::Hypermutation of the immunoglobulin (Ig) genes requires Activation Induced cytidine Deaminase (AID) and transcription, but it remains unclear why other transcribed genes of B cells do not mutate. We describe a reporter transgene crippled by hypermutation when inserted into or near the Ig light chain (IgL) locus of the...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000332

    authors: Blagodatski A,Batrak V,Schmidl S,Schoetz U,Caldwell RB,Arakawa H,Buerstedde JM

    更新日期:2009-01-01 00:00:00

  • Time dependent genetic analysis links field and controlled environment phenotypes in the model C4 grass Setaria.

    abstract::Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed six controlled growth trials of an interspecific Setaria italica x Setaria viridis recombinant inbred line populati...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006841

    authors: Feldman MJ,Paul RE,Banan D,Barrett JF,Sebastian J,Yee MC,Jiang H,Lipka AE,Brutnell TP,Dinneny JR,Leakey ADB,Baxter I

    更新日期:2017-06-23 00:00:00

  • Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.

    abstract::We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-car...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000291

    authors: Windbichler N,Papathanos PA,Crisanti A

    更新日期:2008-12-01 00:00:00

  • Binary addition in a living cell based on riboregulation.

    abstract::Synthetic biology aims at (re-)programming living cells like computers to perform new functions for a variety of applications. Initial work rested on transcription factors, but regulatory RNAs have recently gained much attention due to their high programmability. However, functional circuits mainly implemented with re...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007548

    authors: Rosado A,Cordero T,Rodrigo G

    更新日期:2018-07-19 00:00:00

  • An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans.

    abstract::A crucial step in the development of muscle cells in all metazoan animals is the assembly and anchorage of the sarcomere, the essential repeat unit responsible for muscle contraction. In Caenorhabditis elegans, many of the critical proteins involved in this process have been uncovered through mutational screens focusi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000537

    authors: Meissner B,Warner A,Wong K,Dube N,Lorch A,McKay SJ,Khattra J,Rogalski T,Somasiri A,Chaudhry I,Fox RM,Miller DM 3rd,Baillie DL,Holt RA,Jones SJ,Marra MA,Moerman DG

    更新日期:2009-06-01 00:00:00

  • Adaptive evolution among cytoplasmic piRNA proteins leads to decreased genomic auto-immunity.

    abstract::In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). Expression of genomic TEs is proposed to initiate self regulation by increasing the production of repressive piRNAs, thereby "adap...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008861

    authors: Wang L,Barbash DA,Kelleher ES

    更新日期:2020-06-11 00:00:00

  • Genetic analysis of a novel tubulin mutation that redirects synaptic vesicle targeting and causes neurite degeneration in C. elegans.

    abstract::Neuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans α-tubulin gene mec-12 that trigger...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004715

    authors: Hsu JM,Chen CH,Chen YC,McDonald KL,Gurling M,Lee A,Garriga G,Pan CL

    更新日期:2014-11-13 00:00:00

  • Residues clustered in the light-sensing knot of phytochrome B are necessary for conformer-specific binding to signaling partner PIF3.

    abstract::The bHLH transcription factor, Phytochrome Interacting Factor 3 (PIF3), interacts specifically with the photoactivated, Pfr, form of Arabidopsis phytochrome B (phyB). This interaction induces PIF3 phosphorylation and degradation in vivo and modulates phyB-mediated seedling deetiolation in response to red light. To ide...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000352

    authors: Kikis EA,Oka Y,Hudson ME,Nagatani A,Quail PH

    更新日期:2009-01-01 00:00:00

  • Bayesian multivariate reanalysis of large genetic studies identifies many new associations.

    abstract::Genome-wide association studies (GWAS) have now been conducted for hundreds of phenotypes of relevance to human health. Many such GWAS involve multiple closely-related phenotypes collected on the same samples. However, the vast majority of these GWAS have been analyzed using simple univariate analyses, which consider ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008431

    authors: Turchin MC,Stephens M

    更新日期:2019-10-09 00:00:00

  • Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    abstract::Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000259

    authors: Etheridge SL,Ray S,Li S,Hamblet NS,Lijam N,Tsang M,Greer J,Kardos N,Wang J,Sussman DJ,Chen P,Wynshaw-Boris A

    更新日期:2008-11-01 00:00:00

  • Rfx2 Stabilizes Foxj1 Binding at Chromatin Loops to Enable Multiciliated Cell Gene Expression.

    abstract::Cooperative transcription factor binding at cis-regulatory sites in the genome drives robust eukaryotic gene expression, and many such sites must be coordinated to produce coherent transcriptional programs. The transcriptional program leading to motile cilia formation requires members of the DNA-binding forkhead (Fox)...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006538

    authors: Quigley IK,Kintner C

    更新日期:2017-01-19 00:00:00

  • Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

    abstract::Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigg...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005792

    authors: Federico MB,Vallerga MB,Radl A,Paviolo NS,Bocco JL,Di Giorgio M,Soria G,Gottifredi V

    更新日期:2016-01-14 00:00:00

  • Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing.

    abstract::Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of "modular...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0010034

    authors: Xing Y,Lee CJ

    更新日期:2005-09-01 00:00:00

  • Adaptive diversification in genes that regulate resource use in Escherichia coli.

    abstract::While there has been much recent focus on the ecological causes of adaptive diversification, we know less about the genetic nature of the trade-offs in resource use that create and maintain stable, diversified ecotypes. Here we show how a regulatory genetic change can contribute to sympatric diversification caused by ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030015

    authors: Spencer CC,Bertrand M,Travisano M,Doebeli M

    更新日期:2007-01-19 00:00:00

  • Silencing of DNase Colicin E8 Gene Expression by a Complex Nucleoprotein Assembly Ensures Timely Colicin Induction.

    abstract::Colicins are plasmid-encoded narrow spectrum antibiotics that are synthesized by strains of Escherichia coli and govern intraspecies competition. In a previous report, we demonstrated that the global transcriptional factor IscR, co dependently with the master regulator of the DNA damage response, LexA, delays inductio...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005354

    authors: Kamenšek S,Browning DF,Podlesek Z,Busby SJ,Žgur-Bertok D,Butala M

    更新日期:2015-06-26 00:00:00

  • Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.

    abstract::Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005097

    authors: Simon M,Richard EM,Wang X,Shahzad M,Huang VH,Qaiser TA,Potluri P,Mahl SE,Davila A,Nazli S,Hancock S,Yu M,Gargus J,Chang R,Al-Sheqaih N,Newman WG,Abdenur J,Starr A,Hegde R,Dorn T,Busch A,Park E,Wu J,Schwenzer

    更新日期:2015-03-25 00:00:00

  • Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania.

    abstract::Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete st...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008042

    authors: Inbar E,Shaik J,Iantorno SA,Romano A,Nzelu CO,Owens K,Sanders MJ,Dobson D,Cotton JA,Grigg ME,Beverley SM,Sacks D

    更新日期:2019-05-15 00:00:00

  • Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

    abstract::Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic...

    journal_title:PLoS genetics

    pub_type: 杂志文章,meta分析

    doi:10.1371/journal.pgen.1007813

    authors: Day F,Karaderi T,Jones MR,Meun C,He C,Drong A,Kraft P,Lin N,Huang H,Broer L,Magi R,Saxena R,Laisk T,Urbanek M,Hayes MG,Thorleifsson G,Fernandez-Tajes J,Mahajan A,Mullin BH,Stuckey BGA,Spector TD,Wilson SG,Good

    更新日期:2018-12-19 00:00:00

  • Functional exploration of the IFT-A complex in intraflagellar transport and ciliogenesis.

    abstract::Intraflagellar transport (IFT) particles or trains are composed of IFT-A and IFT-B complexes. To assess the working mechanism of the IFT-A complex in IFT and ciliogenesis, we have analyzed ift43 mutants of Chlamydomnonas in conjunction with mutants of the other IFT-A subunits. An ift43 null mutant or a mutant with a p...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006627

    authors: Zhu B,Zhu X,Wang L,Liang Y,Feng Q,Pan J

    更新日期:2017-02-16 00:00:00

  • Genetic diversity in the interference selection limit.

    abstract::Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004222

    authors: Good BH,Walczak AM,Neher RA,Desai MM

    更新日期:2014-03-27 00:00:00

  • The nucleoside diphosphate kinase gene Nme3 acts as quantitative trait locus promoting non-Mendelian inheritance.

    abstract::The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (> 95%) from heterozygous (t/+) males to their offspring. This phenotype is termed transmission ratio distortion (TRD) and is caused by the interaction of the t-complex...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002567

    authors: Bauer H,Schindler S,Charron Y,Willert J,Kusecek B,Herrmann BG

    更新日期:2012-01-01 00:00:00

  • A catalog of neutral and deleterious polymorphism in yeast.

    abstract::The abundance and identity of functional variation segregating in natural populations is paramount to dissecting the molecular basis of quantitative traits as well as human genetic diseases. Genome sequencing of multiple organisms of the same species provides an efficient means of cataloging rearrangements, insertion,...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000183

    authors: Doniger SW,Kim HS,Swain D,Corcuera D,Williams M,Yang SP,Fay JC

    更新日期:2008-08-29 00:00:00

  • Inducible and reversible Clock gene expression in brain using the tTA system for the study of circadian behavior.

    abstract::The mechanism of circadian oscillations in mammals is cell autonomous and is generated by a set of genes that form a transcriptional autoregulatory feedback loop. While these "clock genes" are well conserved among animals, their specific functions remain to be fully understood and their roles in central versus periphe...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030033

    authors: Hong HK,Chong JL,Song W,Song EJ,Jyawook AA,Schook AC,Ko CH,Takahashi JS

    更新日期:2007-02-23 00:00:00

  • Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network.

    abstract::Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002734

    authors: Pylkäs K,Vuorela M,Otsukka M,Kallioniemi A,Jukkola-Vuorinen A,Winqvist R

    更新日期:2012-01-01 00:00:00

  • Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.

    abstract::Single nucleotide polymorphisms (SNPs) on chromosome 9p21 are associated with coronary artery disease, diabetes, and multiple cancers. Risk SNPs are mainly non-coding, suggesting that they influence expression and may act in cis. We examined the association between 56 SNPs in this region and peripheral blood expressio...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000899

    authors: Cunnington MS,Santibanez Koref M,Mayosi BM,Burn J,Keavney B

    更新日期:2010-04-08 00:00:00

  • RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition.

    abstract::Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001048

    authors: Wang J,Robida-Stubbs S,Tullet JM,Rual JF,Vidal M,Blackwell TK

    更新日期:2010-08-05 00:00:00