Featured
-
-
Article
| Open AccessA quantitative description of Ndc80 complex linkage to human kinetochores
The Ndc80 complex acts as an interface between kinetochores and spindle microtubules, and is recruited to the kinetochore by several different proteins. Suzukiet al. use protein counting techniques and RNA interference to quantify the interaction stoichiometries within this intricate cellular structure.
- Aussie Suzuki
- , Benjamin L. Badger
- & Edward D. Salmon
-
Article
| Open AccessCas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters
Genomic engineering often requires the cloning of long DNA segments that contain large gene clusters. Here, the authors describe an RNA-guided Cas9 nuclease assistedin vitrotechnique that allows the targeted cloning of near-arbitrary, long bacterial genomic sequences of up to 100 kb in a single step.
- Wenjun Jiang
- , Xuejin Zhao
- & Ting F. Zhu
-
Article |
Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process
Damaged DNA is often targeted to nuclear pore complexes for repair. Here, the authors show that kinesin-14 mediates this process ensuring error-prone repair, while perinuclear telomere attachment licenses damaged telomeric loci for this repair and kinesin-14 blocks senescence in the absence of telomerase.
- Daniel K.C. Chung
- , Janet N.Y. Chan
- & Karim Mekhail
-
Article
| Open AccessTwo routes to senescence revealed by real-time analysis of telomerase-negative single lineages
Erosion of telomeres eventually causes replicative senescence, but mechanisms underlying the variability and dynamics of the pathway are not known. Here, the authors examine senescence in single yeast cells with inactivated telomerase to reveal two mechanistically distinct routes to senescence.
- Zhou Xu
- , Emilie Fallet
- & Maria Teresa Teixeira
-
Article
| Open AccessTelomeric G-quadruplexes are a substrate and site of localization for human telomerase
G-quadruplexes formed by four guanine bases in a square planar arrangement in telomeres may prevent extension of this region by telomerase. Here, the authors show that telomerase can localize to and partially unwind and extend G-quadruplexes, suggesting an important biological role for G-quadruplexes.
- Aaron L. Moye
- , Karina C. Porter
- & Tracy M. Bryan
-
Article
| Open AccessTD-60 links RalA GTPase function to the CPC in mitosis
TD-60 (RCC2) structurally resembles a guanine nucleotide exchange factor (GEF), but its target GTPase was unknown. Here Papini et al.show that TD-60 is a GEF for RalA, and that RalA helps to regulate the chromosomal passenger complex and kinetochore–microtubule interactions in mitosis.
- Diana Papini
- , Lars Langemeyer
- & William C. Earnshaw
-
Article
| Open AccessPrediction model for aneuploidy in early human embryo development revealed by single-cell analysis
Aneuploidy may be fatal for the embryo, hence predicting its occurrence is important for successfulin vitrofertilization. Here the authors monitor development of human preimplantation embryos in real-time and correlate the blastomere ploidy with cleavage dynamics and gene expression, identifying 12-transcript signature that determines ploidy.
- Maria Vera-Rodriguez
- , Shawn L. Chavez
- & Carlos Simon
-
Article
| Open AccessSuppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX
ATRX, a chromatin remodelling factor, is mutated in cancers that maintain telomere length by alternative lengthening of telomeres (ALT). Here, the authors show that ectopic expression of ATRX triggers telomere shortening, ALT suppression and reduced replication fork stalling.
- David Clynes
- , Clare Jelinska
- & Richard J. Gibbons
-
Article
| Open AccessConcentration- and chromosome-organization-dependent regulator unbinding from DNA for transcription regulation in living cells
Binding and unbinding of transcription regulators at operator sites regulates gene expression. By single-molecule tracking of metal-sensing regulators, here the authors show that the unbinding kinetics depends on regulator concentration and chromosome condensation, and varies with their metal-binding states.
- Tai-Yen Chen
- , Ace George Santiago
- & Peng Chen
-
Article
| Open AccessSingle-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes
The spatial organization of the genome within the nucleus impacts many processes. Here the authors combine oligo-based DNA FISH with single-molecule super-resolution microscopy to image single-copy genomic regions and, taking advantage of SNPs, distinguish allelic regions of homologous chromosomes.
- Brian J. Beliveau
- , Alistair N. Boettiger
- & Chao-ting Wu
-
Article |
Borealin dimerization mediates optimal CPC checkpoint function by enhancing localization to centromeres and kinetochores
Borealin is a subunit of the chromosomal passenger complex that prevents premature mitosis before spindle assembly is complete. Bekier et al.show that Borealin mediates recruitment of this complex to both kinetochores and centromeres via distinct mechanisms, both of which depend on Borealin dimerization.
- Michael E. Bekier
- , Travis Mazur
- & William R. Taylor
-
Article |
Prevalent and distinct spliceosomal 3′-end processing mechanisms for fungal telomerase RNA
In fission yeast, the telomerase RNA (TER) is produced through inhibition of the second step in splicing, resulting in spliceosomal cleavage. Here, the authors show that the inhibition of splicing is a conserved principle in fungal TER maturation that uses distinct molecular mechanisms across species.
- Xiaodong Qi
- , Dustin P. Rand
- & Julian J. -L. Chen
-
Article
| Open AccessDiverse mechanisms for spliceosome-mediated 3′ end processing of telomerase RNA
In fission yeast, the telomerase RNA (TER) is produced through spliceosomal cleavage. Here, Kannan et al. find that spliceosome-generated 3′ ends also occurs in other fungal TERs using distinct molecular mechanisms, suggesting multiple origins for this type of TER maturation pathway.
- Ram Kannan
- , Rachel M. Helston
- & Peter Baumann
-
Article
| Open AccessCentromeric binding and activity of Protein Phosphatase 4
Many cellular processes, including the cell division cycle, require concerted action of protein kinases and phosphatases. Here Lipinszki et al. present a crystal structure of the Drosophilaphosphoprotein phosphatase 4 subunit, Falafel, in complex with the centromeric protein CENP-C, and reveal a new recognition mode for this phosphatase.
- Zoltan Lipinszki
- , Stephane Lefevre
- & Marcin R. Przewloka
-
Article |
Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction
Short telomeres are risk factors for age-associated diseases such as cardiopathies. Here the authors show that cardiac reactivation of telomerase, the telomere-elongating enzyme whose expression is normally silenced postnatally, mitigates the consequences of myocardial infarction in adult mice.
- Christian Bär
- , Bruno Bernardes de Jesus
- & Maria A. Blasco
-
Article
| Open AccessTRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends
The shortening of telomeres—a structure that protects chromosome ends—is associated with cellular aging. Here, Wood et al.present evidence that interaction between the telomere-binding protein TRF2 and lamin A/C facilitates the formation of interstitial t-loops and stabilizes telomeres.
- Ashley M. Wood
- , Jannie M. Rendtlew Danielsen
- & Steven T. Kosak
-
Article |
PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase
Telomere maintenance requires proper termination of telomere replication at G2/M cell cycle stage. Here, Shen et al.show that termination of telomere replication requires PP2A phosphatase and Aurora kinase, which work independently but additively to remove active telomerase from telomeres.
- Zih-Jie Shen
- , Pang-Hung Hsu
- & Shu-Chun Teng
-
Article |
Functional characterization of the TERRA transcriptome at damaged telomeres
Telomere uncapping in senescent cells is accompanied by loss of the TRF2 telomere capping factor and upregulation of the long noncoding RNA TERRA. Here the authors characterize the TERRA transcriptome and show that TERRA upregulation may promote SUV39H1 recruitment, H3K9 trimethylation and telomere end-to-end fusions.
- Antonio Porro
- , Sascha Feuerhahn
- & Joachim Lingner
-
Article
| Open AccessDirect interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole
Centrosome duplication requires a cartwheel-shaped protein complex containing the protein HsSAS-6, which acts as a template for centriole assembly. Ohta et al.show that HsSAS-6 is recruited to this structure by STIL and Plk4, and reveal that Plk4 phosphorylates STIL, stabilizing its interaction with HsSAS-6.
- Midori Ohta
- , Tomoko Ashikawa
- & Daiju Kitagawa
-
Article
| Open AccessRNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells
A subset of cancers maintains telomere length independently of telomerase by activating alternative lengthening of telomeres (ALT) pathways. Here the authors show that RNaseH1 modulates telomeric homologous recombination frequencies in ALT cells by regulating the levels of RNA–DNA hybrids between TERRA and telomeric DNA.
- Rajika Arora
- , Yongwoo Lee
- & Claus M. Azzalin
-
Article |
Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA
The enzymes Sae2 and Sgs1 regulate telomere maintenance in yeast cells that are telomerase-positive or -negative, but how they do this is unclear. Here the authors show that Sae2 and Sgs1 facilitate telomere replication in telomerase-positive cells, but generate single-stranded DNA at eroded telomeres in telomerase-negative cells.
- Julien Hardy
- , Dmitri Churikov
- & Marie-Noëlle Simon
-
Article
| Open AccessGlucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice
Shortened telomeres and reduced mitochondrial biogenesis are cellular hallmarks of ageing. Here, Missios et al.show that old mice with telomere dysfunction have an increased energetic demand that cannot be met unless mice are fed a glucose-rich diet, which improves energy metabolism and extends lifespan.
- Pavlos Missios
- , Yuan Zhou
- & K. Lenhard Rudolph
-
Article
| Open AccessIdentification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes
Telomeric RNAs (TERRAs) are known to be transcribed towards the telomere from subtelomeric regions, however, their precise genomic origins are unclear. Here López de Silanes et al.identify novel transcripts that originate from the subtelomeric region of mouse chromosome 18 and behave as bona fide TERRAs.
- Isabel López de Silanes
- , Osvaldo Graña
- & Maria A Blasco
-
Article |
The condensin component NCAPG2 regulates microtubule–kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores
Polo-like kinase 1 (PLK1) regulates the spindle assembly checkpoint and is recruited to prometaphase kinetochores. Kim et al.show that the condensin subunit NCAPG2 is required for stable interaction of PLK1 with kinetochores and for proper chromosome segregation.
- Jae Hyeong Kim
- , Jaegal Shim
- & Kyung-Tae Kim
-
Article |
Coordinated DNA dynamics during the human telomerase catalytic cycle
Telomerase reverse transcriptase extends the ends of linear chromosomes with the aid of an integral RNA subunit. Here, Parks and Stone characterize the translocation kinetics of telomerase identifying distinct steps important for the processivity of the enzyme.
- Joseph W. Parks
- & Michael D. Stone
-
Article |
Persistent super-diffusive motion of Escherichia coli chromosomal loci
In bacteria, chromosomal architecture exhibits spatial and temporal fluctuations, which affect cellular functions. Here, Javer et al. use high-resolution tracking of chromosomal loci in E. colito uncover rare events of unusually large and fast movements, providing new insight into bacterial chromosome dynamics.
- Avelino Javer
- , Nathan J. Kuwada
- & Marco Cosentino Lagomarsino
-
Article
| Open AccessRegulation of human telomerase splicing by RNA:RNA pairing
Telomerase activity can be regulated by alternative splicing of its catalytic subunit TERT. Here, Wong et al. demonstrate that TERTsplicing is regulated via RNA:RNA pairing of repetitive intronic sequences with the pre-mRNA, thus revealing a new function for conserved elements embedded within introns.
- Mandy S. Wong
- , Jerry W. Shay
- & Woodring E. Wright
-
Article |
A quantitative telomeric chromatin isolation protocol identifies different telomeric states
The protein composition of telomeres changes during development, aging, tumourigenesis and in telomere syndromes. Here, the authors develop a quantitative telomeric chromatin isolation protocol (QTIP) to analyse and quantitatively compare telomeric chromatin of different cell populations.
- Larissa Grolimund
- , Eric Aeby
- & Joachim Lingner
-
Article |
Short-time movement of E. coli chromosomal loci depends on coordinate and subcellular localization
The spatial and temporal organization of bacterial chromosomes is important for many cellular functions. Using high-precision measurements of fluorescently labelled chromosomal loci, Javer et al.demonstrate variation in the dynamics of different chromosomal sites, which may either be due to differential organization of the chromosome or spatial variation in molecular noise.
- Avelino Javer
- , Zhicheng Long
- & Marco Cosentino Lagomarsino
-
Article
| Open AccessTelomeres shorten at equivalent rates in somatic tissues of adults
Telomere shortening as a result of cell proliferation has been implicated in human ageing. Here, Daniali and colleagues show that telomere length and the rate of age-dependent shortening vary between adults but are similar within tissues of the same individual.
- Lily Daniali
- , Athanase Benetos
- & Abraham Aviv
-
Article
| Open AccessTelomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
Irreparable DNA damage leads to apoptosis or senescence. Hewittet al. show that, in response to genotoxic or oxidative stress, DNA damage occurs predominantly at telomere associated foci, which accumulate with age in vivo, irrespective of telomerase activity.
- Graeme Hewitt
- , Diana Jurk
- & João F. Passos
-
Article |
SIRT6 is required for maintenance of telomere position effect in human cells
Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.
- Ruth I. Tennen
- , Dennis J. Bua
- & Katrin F. Chua
-
Article |
Cyclin B-dependent kinase 1 regulates human TRF1 to modulate the resolution of sister telomeres
TRF1 is a telomere binding protein involved in sister telomere cohesion. In this study, the ability of TRF1 to bind to telomeres in mitosis is inhibited by cyclin-dependent kinase 1-mediated phosphorylation, which may facilitate sister telomere resolution during mitosis.
- Megan McKerlie
- & Xu-Dong Zhu
-
Article
| Open AccessStructure and Scm3-mediated assembly of budding yeast centromeric nucleosomes
There is debate about the structural organization of the yeast centromeric nucleosome and the role of the nonhistone protein Scm3 in its assembly. Dechassaet al.find that yeast centromeric nucleosomes organize DNA in a left-handed superhelix, and show that Scm3 is a specific nucleosome assembly factor.
- Mekonnen Lemma Dechassa
- , Katharina Wyns
- & Karolin Luger
-
Article |
Larger mitochondrial DNA than Y-chromosome differences between matrilocal and patrilocal groups from Sumatra
Matrilocal and patrilocal populations are predicted to have greater genetic diversity in mitochondrial DNA and the Y-chromosome, respectively. Here, no difference in the diversity of the Y-chromosome was found in two such groups, suggesting that local diversity was caused by male gene flow in expanding populations.
- Ellen Dröfn Gunnarsdóttir
- , Madhusudan R. Nandineni
- & Mark Stoneking
-
Article |
TERRA transcripts are bound by a complex array of RNA-binding proteins
Recent work has revealed that the TTAGGG DNA repeats of telomeres are transcribed to form 'TERRA'. In this study, a set of RNA-binding proteins are shown to bind TERRA transcripts, altering the location of these transcripts at telomeres and regulating telomere abundance and length.
- Isabel López de Silanes
- , Martina Stagno d'Alcontres
- & Maria A Blasco