Chromosomes

  • Article
    | Open Access

    DNA:RNA hybrids (R-loops) are products of transcription that impact genome integrity and gene expression. Here the authors reveal a mechanism for regulating R-loops in a ubiquitination-dependent manner controlled by the activities of USP11 and KEAP1

    • Mateusz Jurga
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy
  • Article
    | Open Access

    MAD2L2 — a member of the shieldin complex — is known to play important roles in DNA repair. Here the authors demonstrate how MAD2L2 dimerization mediated through SHLD2 participates in shieldin assembly and function.

    • Inge de Krijger
    • , Bastian Föhr
    •  & Jacqueline J. L. Jacobs
  • Article
    | Open Access

    Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an ‘open’ to a ‘closed’ conformation.

    • Marcin J. Szafran
    • , Tomasz Małecki
    •  & Dagmara Jakimowicz
  • Article
    | Open Access

    Streptomyces bacteria have a linear chromosome, with core genes located in the central region and gene clusters for specialized metabolite biosynthesis found in the ‘arms’. Here, Lioy et al. show that such chromosome structure correlates with genetic compartmentalization, and the onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture.

    • Virginia S. Lioy
    • , Jean-Noël Lorenzi
    •  & Stéphanie Bury-Moné
  • Article
    | Open Access

    Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.

    • Aleksandra Lezaja
    • , Andreas Panagopoulos
    •  & Matthias Altmeyer
  • Article
    | Open Access

    TERRA RNA has previously been linked to Alternative lengthening of telomeres (ALT). Here the authors developed a tool to rapidly inhibit TERRA transcription from different chromosome ends in an ALT cell line to show that TERRA transcription actively promotes break induced replication (BIR) and destabilizes telomere integrity in ALT cells.

    • Bruno Silva
    • , Rajika Arora
    •  & Claus M. Azzalin
  • Article
    | Open Access

    BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.

    • Jekaterina Vohhodina
    • , Liana J. Goehring
    •  & David M. Livingston
  • Article
    | Open Access

    The genome-wide investigation of chromatin organization enables insights into global gene expression control. Here, the authors present a computationally efficient method for the analysis of chromatin organization data and use it to recover principles of 3D organization across conditions.

    • Merve Sahin
    • , Wilfred Wong
    •  & Christina S. Leslie
  • Article
    | Open Access

    Long non coding RNA TERRA transcripts can form R-loops at chromosome ends. Here, the authors reveal a role for the helicase RTEL in affecting TERRA levels and localization.

    • Fiorella Ghisays
    • , Aitor Garzia
    •  & John H. J. Petrini
  • Article
    | Open Access

    How mammalian genomes are packaged and the heritability of structural variations in genome folding is incomplete. Here, the authors investigate the impact of chromosomal fusions on three-dimensional genome topology and meiotic recombination, highlighting the implications of large-scale genome reorganizations on genome function, evolution, and fertility.

    • Covadonga Vara
    • , Andreu Paytuví-Gallart
    •  & Aurora Ruiz-Herrera
  • Article
    | Open Access

    Different proteins localised at telomeres ensure chromosome end stability to prevent double strand-end break recognition. Here the authors provide new insight into how in S. cerevisiae the interaction between Rif2 and Rad50 inhibits MRX functions at telomeres.

    • Florian Roisné-Hamelin
    • , Sabrina Pobiega
    •  & Stéphane Marcand
  • Article
    | Open Access

    Telomeres, tandem repeats at the ends of linear chromosomes, have evolved to deal with the end replication and end protection. Using a proteomics approach, the authors identify TEBP-1 and TEBP-2, two double-stranded binding proteins which together are required for fertility. Despite being paralogs, they have distinct individual effects on telomere dynamics; TEBP-1 and TEBP-2 are part of a telomeric complex also containing POT-1.

    • Sabrina Dietz
    • , Miguel Vasconcelos Almeida
    •  & Falk Butter
  • Article
    | Open Access

    Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers that have been associated with mutations in ATRX. Here the authors reveal a functional role of histone demethylases KDM4B in regulating ALT activation.

    • M. Udugama
    • , L. Hii
    •  & L. H. Wong
  • Article
    | Open Access

    Telomere crisis has been shown to induce chromothripsis and breakage fusion bridge (BFB) cycles in vitro. Here, the authors show that telomere crisis generates a much broader spectrum of structural variations, implying that cancers without chromothripsis and BFB cycles could have emerged from telomere crisis.

    • Sally M. Dewhurst
    • , Xiaotong Yao
    •  & Marcin Imieliński
  • Article
    | Open Access

    The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, the authors develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus.

    • Joris J. B. Messelink
    • , Muriel C. F. van Teeseling
    •  & Chase P. Broedersz
  • Article
    | Open Access

    During differentiation, chromosome conformation is remodelled to support lineage-specific transcriptional programs. Here, the authors characterise chromosome conformational changes in B lymphocytes as they differentiate into plasma cells, and provide evidence that chromosome reconfiguration occurs prior to DNA replication and mitosis and guides gene expression that controls differentiation.

    • Wing Fuk Chan
    • , Hannah D. Coughlan
    •  & Rhys S. Allan
  • Article
    | Open Access

    Telomeres can be maintained by a telomerase-independent mechanism called an alternative lengthening of telomeres (ALT). Here the authors use mouse Terc (telomerase RNA) knockout embryonic cells and provide longitudinal analysis of ALT telomeres maintained with non-telomeric sequences.

    • Chuna Kim
    • , Sanghyun Sung
    •  & Junho Lee
  • Article
    | Open Access

    Pyruvate kinase phosphorylates histone H3T11 (H3pT11) and represses gene expression by forming a large complex SESAME (Serine-responsive SAM-containing Metabolic Enzyme). Here the authors show that SESAME-catalyzed H3pT11 regulates telomere silencing by promoting Sir2 binding at telomeres and preventing autophagy-mediated Sir2 degradation.

    • Shihao Zhang
    • , Xilan Yu
    •  & Shanshan Li
  • Article
    | Open Access

    ~15% of cancers induce alternative lengthening of telomeres (ALT) to activate telomere maintenance. Here, the authors reveal that infection with Kaposi’s sarcoma herpesvirus (KSHV) induces acquisition of ALT-like features in previously non-ALT cell lines.

    • Timothy P. Lippert
    • , Paulina Marzec
    •  & Simon J. Boulton
  • Article
    | Open Access

    The kinetochore is a multi-complex structure that helps attach chromosomes to spindle microtubules, ensuring accurate chromosome segregation during cell division. Kinetochores are thought to be evolutionarily conserved, but which components are conserved is unclear. Here, the authors report that some members of the fungal phylum of Basidomycota lack many conventional kinetochore linker proteins. Instead, they possess a human Ki67-like protein that bridges the outer part of the kinetochore to centromere DNA, which may compensate for the loss of a conventional linker.

    • Shreyas Sridhar
    • , Tetsuya Hori
    •  & Kaustuv Sanyal
  • Article
    | Open Access

    Genomic aberrations disrupting chromosome spatial domains can lead to disease. Here, the authors investigate the impact of DNA damage response and repair on 3D genome folding, comparing wild type cells and ataxia telangiectasia mutated patient cells, and characterise both cell type-specific and shared changes to genome organization during the response to damage.

    • Jacob T. Sanders
    • , Trevor F. Freeman
    •  & Rachel Patton McCord
  • Article
    | Open Access

    The boundaries of topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. Here the authors find that CTCF positions cohesin through its N-terminus but does not control its overall binding dynamics on chromatin, and show how the orientation of CTCF binding sites translates into genome folding patterns.

    • Elphège P. Nora
    • , Laura Caccianini
    •  & Benoit G. Bruneau
  • Article
    | Open Access

    Telomerase enzymes add telomeric repeats to the end of linear chromosomes. Here the authors reveal mechanisms by which oxidized dNTPs and therapeutic dNTPs inhibit telomerase-mediated telomere elongation.

    • Samantha L. Sanford
    • , Griffin A. Welfer
    •  & Patricia L. Opresko
  • Article
    | Open Access

    Single molecule force measurements have shed light on dynamic biological events, but rare events escape notice owing to low throughput of the methods. Here, the authors combine an array of magnetic tweezers with lateral flow to increase throughput 100-fold, and detect rare DNA breaks induced by gyrase.

    • Rohit Agarwal
    •  & Karl E. Duderstadt
  • Article
    | Open Access

    Centromeres are the sites of kinetochore and inner centromere formation, which can be epigenetically regulated. Here, the authors reveal a role for the lymphocyte specific helicase LSH/Hells associated with pericentric heterochromatin formation in centromere stability and chromosome segregation at meiotic kinetochores.

    • Claudia Baumann
    • , Wei Ma
    •  & Rabindranath De La Fuente
  • Article
    | Open Access

    Self-propagating drives allow for non-Mendelian inheritance. Here the authors use CRISPR to build a chromosome drive, showing elimination of entire chromosomes, endoreduplication of desired chromosomes and enabling preferential transmissions of complex genetic traits on a chromosomal scale in yeast.

    • Hui Xu
    • , Mingzhe Han
    •  & Ying-Jin Yuan
  • Article
    | Open Access

    Meiosis-specific cohesins and the synaptonemal complex are essential for meiotic chromosome structure and function. Here the authors show that continued surveillance of these chromosome structures controls meiotic progression by regulating CHK-2, a master regulator of pairing and recombination.

    • Maikel Castellano-Pozo
    • , Sarai Pacheco
    •  & Enrique Martinez-Perez
  • Article
    | Open Access

    Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, the authors isolate native chromosomes from metaphase-arrested cells and perform LC-MS/MS to identify chromosome-bound proteins in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.

    • Dounia Djeghloul
    • , Bhavik Patel
    •  & Amanda G. Fisher
  • Article
    | Open Access

    While R-loops can alter cell homeostasis, it is unclear what determines their toxicity. Here, the authors, by using Top1 knockdown as a tool to enhance the formation of R-loops at certain genomic sites, reveal and characterize a proportion of R-loops that are more toxic to the cell by causing DNA damage.

    • Alexy Promonet
    • , Ismaël Padioleau
    •  & Philippe Pasero
  • Article
    | Open Access

    Telomere function is regulated by the telomere repeat binding proteins TRF1 and TRF2. Here the authors show that decreased levels of TRF1 proteins at shortened telomeres in aged human cells results in persistent telomere cohesion, protecting from premature senescence.

    • Kameron Azarm
    • , Amit Bhardwaj
    •  & Susan Smith
  • Article
    | Open Access

    CENP-A is a stable centromere mark, although active transcription poses a potential threat for retaining CENP-A through chromatin remodeling and nucleosome eviction. Here, the authors show that maintenance of the centromeric mark is preserved by Spt6, which recycles CENP-A nucleosomes.

    • Georg O. M. Bobkov
    • , Anming Huang
    •  & Patrick Heun
  • Article
    | Open Access

    The three-dimensional architecture of the genome affects genomic functions. Here, the authors developed Multiplexed Imaging of Nucleome Architectures to measure multiscale chromatin folding, RNA profiles, and associations of numerous genomic regions with nuclear lamina and nucleoli in the same, single cells in heterogeneous tissue.

    • Miao Liu
    • , Yanfang Lu
    •  & Siyuan Wang
  • Article
    | Open Access

    B chromosomes are supernumerary chromosomes exhibiting dramatic differences between different organs in same species. Here, the authors show programmed B chromosome elimination in goatgrass starts at the onset of embryo differentiation by nondisjunction of chromatids, anaphase lagging, and ends with the degradation of micronucleated DNA.

    • Alevtina Ruban
    • , Thomas Schmutzer
    •  & Andreas Houben
  • Article
    | Open Access

    The nuclear pore complex components, nucleoporins, have been proposed to mediate spatial and temporal organization of chromatin. Here, the authors show that Nucleoporin 153 interacts with CTCF and cohesin, and mediates their binding across cis-regulatory elements and TAD boundaries in mouse embryonic stem cells.

    • Shinichi Kadota
    • , Jianhong Ou
    •  & Eda Yildirim
  • Article
    | Open Access

    Pop1 and 6 are subunits of RNase P and RNase MRP, which process ribosomal and tRNAs. The authors show that when Pop1 and 6 are impaired, the telomerase subunit Est1 binds telomerase RNA at normal levels, but the binding is unstable. As a result, nuclear import of the telomerase holoenzyme is inhibited.

    • P. Daniela Garcia
    • , Robert W. Leach
    •  & Virginia A. Zakian
  • Article
    | Open Access

    The second messenger c-di-GMP modulates multiple responses to environmental and cellular signals in bacteria. Here, Skotnicka et al. identify a protein that binds c-di-GMP and contributes to chromosome organization and segregation in Myxococcus xanthus, with DNA-binding activity regulated by c-di-GMP.

    • Dorota Skotnicka
    • , Wieland Steinchen
    •  & Lotte Søgaard-Andersen
  • Article
    | Open Access

    The BRCA2 tumour suppressor protein is known to play an important role in homologous recombination. Here the authors reveal how the phosphorylation of BRCA2 by Polo-like kinase 1 (PLK1) contributes to the regulation of mitosis.

    • Åsa Ehlén
    • , Charlotte Martin
    •  & Aura Carreira
  • Article
    | Open Access

    Centromeres are a self-propagating chromatin structure that feature nucleosomes containing histone H3 variant CENP-A. Here, the authors screen for factors that play a role in CENP-A chromatin maintenance, finding that SUMO-protease SENP6 controls inheritance of chromatin bound CENP-A and is required for the maintenance of the centromere and kinetochore complex.

    • Sreyoshi Mitra
    • , Dani L. Bodor
    •  & Lars E. T. Jansen
  • Article
    | Open Access

    Major effect loci controlling natural, heritable variation in telomere length are not known. Here, the authors use QTL mapping and transgenic manipulations in Arabidopsis to implicate the rRNA-processing genes NOP2A and RPL5 in telomere length set point regulation in this model species.

    • Liliia R. Abdulkina
    • , Callie Kobayashi
    •  & Eugene V. Shakirov
  • Article
    | Open Access

    In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

    • Koustav Pal
    • , Mattia Forcato
    •  & Francesco Ferrari
  • Article
    | Open Access

    The chromosomal kinase JIL-1 is responsible for interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from heterochromatinisation. Here, the authors show that JIL-1 is stabilized and anchored to active genes and telomeric transposons by JASPer, which binds to H3K36me3 nucleosomes via its PWWP domain.

    • Christian Albig
    • , Chao Wang
    •  & Catherine Regnard