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CST–polymerase α-primase solves a second telomere end-replication problem
Incomplete duplication of the C-rich telomeric repeat strand by lagging-strand DNA synthesis is counteracted by DNA synthesis mediated by CST–polymerase α-primase.
- Hiroyuki Takai
- , Valentina Aria
- & Titia de Lange
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Article |
The complete sequence of a human Y chromosome
We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.
- Arang Rhie
- , Sergey Nurk
- & Adam M. Phillippy
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Article
| Open Access
Non-cell-autonomous cancer progression from chromosomal instability
Chromosomal instability in cancer is linked to endoplasmic reticulum stress signalling, immune suppression and metastasis, which is mediated by the cGAS–STING pathway, suppression of which can reduce metastasis.
- Jun Li
- , Melissa J. Hubisz
- & Samuel F. Bakhoum
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Article
| Open Access
Einkorn genomics sheds light on history of the oldest domesticated wheat
Around 1% of the A subgenome of modern bread wheat (Triticum aestivum) originates from einkorn (Triticum monococcum), the first domesticated wheat species.
- Hanin Ibrahim Ahmed
- , Matthias Heuberger
- & Simon G. Krattinger
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Article |
Y chromosome loss in cancer drives growth by evasion of adaptive immunity
Loss of the Y chromosome in tumour cells is associated with a poor prognosis for patients with bladder cancer by causing local T cell exhaustion, which also increases the response to immune checkpoint blockade therapy.
- Hany A. Abdel-Hafiz
- , Johanna M. Schafer
- & Dan Theodorescu
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Mitotic tethering enables inheritance of shattered micronuclear chromosomes
Chromothriptically produced pieces of a micronucleated chromosome are shown to be tethered together in mitosis by a protein complex consisting of MDC1, TOPBP1 and CIP2A, thus enabling their inheritance by a single daughter cell.
- Prasad Trivedi
- , Christopher D. Steele
- & Don W. Cleveland
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Article |
Break-induced replication orchestrates resection-dependent template switching
Break-induced telomere synthesis initiates recruitment of the SNM1A nuclease, which promotes DNA end resection that in turn allows template switching to enable bypass of lesions.
- Tianpeng Zhang
- , Yashpal Rawal
- & Roger A. Greenberg
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Article
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Heritable transcriptional defects from aberrations of nuclear architecture
Micronuclei, which are common features of nuclei in cancer cells, can generate heritable sources of transcriptional suppression, a finding that establishes an inherent relationship between chromosomal instability and variation in chromatin state and gene expression.
- Stamatis Papathanasiou
- , Nikos A. Mynhier
- & David Pellman
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Article
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Epigenetic dysregulation from chromosomal transit in micronuclei
Missegregated chromosomes that are sequestrated in micronuclei are subject to changes in histone modifications leading to abnormalities in chromatin accessibility that remain long after the chromosomes have been reincorporated into the primary nucleus.
- Albert S. Agustinus
- , Duaa Al-Rawi
- & Samuel F. Bakhoum
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Article
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Recombination between heterologous human acrocentric chromosomes
Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.
- Andrea Guarracino
- , Silvia Buonaiuto
- & Erik Garrison
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Article
| Open Access
The Smc5/6 complex is a DNA loop-extruding motor
Using single-molecule imaging, the authors show that Smc5/6 forms DNA loops by extrusion, which establishes DNA loop extrusion as a conserved mechanism among eukaryotic SMC complexes.
- Biswajit Pradhan
- , Takaharu Kanno
- & Eugene Kim
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Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats
Epstein–Barr Virus (EBV) nuclear antigen 1 is shown to induce breakage of a fragile site on chromosome 11 by binding to a cluster of EBV-like imperfect palindromic repeats.
- Julia Su Zhou Li
- , Ammal Abbasi
- & Don W. Cleveland
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Article
| Open Access
The molecular evolution of spermatogenesis across mammals
Evolutionary analyses of single-nucleus transcriptome data for testes from 11 species are reported, illuminating the molecular evolution of spermatogenesis and associated forces, and providing a resource for investigating the testis across mammals.
- Florent Murat
- , Noe Mbengue
- & Henrik Kaessmann
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Article
| Open Access
Semi-automated assembly of high-quality diploid human reference genomes
Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.
- Erich D. Jarvis
- , Giulio Formenti
- & Karen H. Miga
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Columnar structure of human telomeric chromatin
Cryogenic electron microscopy analyses reveal a new, compact structure of telomeric chromatin, providing mechanistic insight into telomere maintenance and function.
- Aghil Soman
- , Sook Yi Wong
- & Lars Nordenskiöld
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A mitotic chromatin phase transition prevents perforation by microtubules
Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.
- Maximilian W. G. Schneider
- , Bryan A. Gibson
- & Daniel W. Gerlich
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Article
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Nuclear chromosome locations dictate segregation error frequencies
Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, chromosomes are shown to have different segregation error frequencies that result in non-random aneuploidy landscapes.
- Sjoerd J. Klaasen
- , My Anh Truong
- & Geert J. P. L. Kops
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Matters Arising |
Limitations of gamete sequencing for crossover analysis
- Carl Veller
- , Shunxin Wang
- & Nancy Kleckner
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Article
| Open Access
Island-specific evolution of a sex-primed autosome in a sexual planarian
Assembly and analysis of the Schmidtea mediterranea genome indicate that this planarian’s chromosome 1 may be evolving into a sex chromosome.
- Longhua Guo
- , Joshua S. Bloom
- & Leonid Kruglyak
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Article
| Open Access
MCM complexes are barriers that restrict cohesin-mediated loop extrusion
Single-nucleus Hi-C of embryos, polymer simulations and single-molecule imaging collectively reveal that MCM complexes influence genome folding and gene expression by impeding DNA loop extrusion.
- Bart J. H. Dequeker
- , Matthias J. Scherr
- & Kikuë Tachibana
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Article |
Breakage of cytoplasmic chromosomes by pathological DNA base excision repair
DNA damage during chromothripsis is caused by deoxyinosine formation on accumulated RNA–DNA hybrids in micronuclei that are then recognized by N-methyl-purine DNA glycosylase and cleaved by apurinic/apyrimidinic endonuclease.
- Shangming Tang
- , Ema Stokasimov
- & David Pellman
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Targeting Xist with compounds that disrupt RNA structure and X inactivation
A molecule identified in a screen for compounds that bind the non-coding mouse RNA Xist blocks Xist-dependent X-chromosome inactivation, demonstrating the utility of this approach for identifying drugs that target RNA.
- Rodrigo Aguilar
- , Kerrie B. Spencer
- & Jeannie T. Lee
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Activation of homologous recombination in G1 preserves centromeric integrity
Centromeres are able to recruit the homologous recombination machinery during G1 via CENP-A and HJURP, thereby preserving centromeric integrity even in the absence of a sister chromatid.
- Duygu Yilmaz
- , Audrey Furst
- & Evi Soutoglou
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NORAD-induced Pumilio phase separation is required for genome stability
The noncoding RNA NORAD maintains genome stability in mammalian cells by sequestering Pumilio proteins in phase-separated compartments.
- Mahmoud M. Elguindy
- & Joshua T. Mendell
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Structures of telomerase at several steps of telomere repeat synthesis
Cryo-electron microscopy structures of Tetrahymena telomerase with telomeric DNA at several steps of nucleotide addition provide insights into the structural basis of telomere repeat synthesis.
- Yao He
- , Yaqiang Wang
- & Juli Feigon
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Article |
Structure of human telomerase holoenzyme with bound telomeric DNA
A high-resolution structure of human telomerase bound to telomeric DNA reveals details of telomerase assembly and its active site, and sheds light on how mutations alter telomerase function.
- George E. Ghanim
- , Adam J. Fountain
- & Thi Hoang Duong Nguyen
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Article
| Open Access
The structure, function and evolution of a complete human chromosome 8
The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.
- Glennis A. Logsdon
- , Mitchell R. Vollger
- & Evan E. Eichler
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Article |
Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8
The meiotic proteins Spo11 and Rec8, which ensure meiotic recombination and reductional chromosome segregation, have additional activities that challenge centromere stability by promoting centromeric nucleosome remodelling in both fission yeast and human cells.
- Haitong Hou
- , Eftychia Kyriacou
- & Julia Promisel Cooper
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Article |
Chromothripsis drives the evolution of gene amplification in cancer
Chromothripsis—a process during which chromosomes are ‘shattered’—drives the evolution of gene amplification and subsequent drug resistance in cancer cells.
- Ofer Shoshani
- , Simon F. Brunner
- & Don W. Cleveland
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TRF2-independent chromosome end protection during pluripotency
Experiments in mouse pluripotent embryonic and epiblast stem cells show that TRF2 is dispensable for telomere protection specifically specifically in the pluripotent cells that form during early embryonic development, when cells form T-loops independently of this protein.
- Phil Ruis
- , David Van Ly
- & Simon J. Boulton
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TRF2-mediated telomere protection is dispensable in pluripotent stem cells
Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation.
- Marta Markiewicz-Potoczny
- , Anastasia Lobanova
- & Eros Lazzerini Denchi
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Article |
RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.
- Marianna Feretzaki
- , Michaela Pospisilova
- & Joachim Lingner
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Article |
Conformation of sister chromatids in the replicated human genome
Modified chromosome conformation capture (Hi-C) technology is used to characterize the interactions between sister chromatids, despite their identical DNA sequences.
- Michael Mitter
- , Catherina Gasser
- & Daniel W. Gerlich
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Article |
Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly
The surfactant-like protein Ki-67 mediates the clustering of chromosomes during mitotic exit, which displaces large cytoplasmic molecules from the future nuclear space and thus enables the separation of cytoplasmic and nuclear components before the nuclear envelope reforms.
- Sara Cuylen-Haering
- , Mina Petrovic
- & Daniel W. Gerlich
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Article |
Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X–Y recombination.
- Laurent Acquaviva
- , Michiel Boekhout
- & Scott Keeney
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Article |
Multilayered mechanisms ensure that short chromosomes recombine in meiosis
Several mechanisms regulate the distribution of double-strand breaks during meiosis in Saccharomyces cerevisiae, ensuring that the shortest chromosomes are able to successfully recombine.
- Hajime Murakami
- , Isabel Lam
- & Scott Keeney
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Article |
Convergent genes shape budding yeast pericentromeres
The three-dimensional structure of pericentromeres in budding yeast is defined by convergent genes, which mark pericentromere borders and trap cohesin complexes loaded at centromeres, generating an architecture that allows correct chromosome segregation.
- Flora Paldi
- , Bonnie Alver
- & Adele L. Marston
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Article |
DNA-loop extruding condensin complexes can traverse one another
Single-molecule visualization shows that condensin—a motor protein that extrudes DNA in one direction only—can encounter and pass a second condensin molecule to form a new type of DNA loop that gathers DNA from both sides.
- Eugene Kim
- , Jacob Kerssemakers
- & Cees Dekker
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Article |
Key role for CTCF in establishing chromatin structure in human embryos
The chromatin regulator CTCF has key roles in the gradual development of hierarchical chromatin structure during human embryogenesis.
- Xuepeng Chen
- , Yuwen Ke
- & Zi-Jiang Chen
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Article |
CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle
A phospho-switch is identified in the shelterin subunit TRF2 that regulates transient recruitment of the RTEL1 helicase to, and release from, telomeres, and provides a narrow window during which RTEL1 can unwind t-loops to facilitate telomere replication.
- Grzegorz Sarek
- , Panagiotis Kotsantis
- & Simon J. Boulton
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Letter |
Heterochromatin drives compartmentalization of inverted and conventional nuclei
Attractions between heterochromatic regions are essential for phase separation of the active and inactive genome in inverted and conventional nuclei, whereas chromatin–lamina interactions are necessary to build the conventional genomic architecture from these segregated phases.
- Martin Falk
- , Yana Feodorova
- & Leonid A. Mirny
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Article |
Total synthesis of Escherichia coli with a recoded genome
High-fidelity convergent total synthesis is used to produce
Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.- Julius Fredens
- , Kaihang Wang
- & Jason W. Chin
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Letter |
Autophagic cell death restricts chromosomal instability during replicative crisis
Cell death during replicative crisis involves autophagy induced by telomere dysfunction.
- Joe Nassour
- , Robert Radford
- & Jan Karlseder
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Brief Communications Arising |
Inter-homologue repair in fertilized human eggs?
- Dieter Egli
- , Michael V. Zuccaro
- & Maria Jasin
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Article |
Creating a functional single-chromosome yeast
Successive fusion of yeast chromosomes is used to produce a single-chromosome strain that is viable, albeit with slightly reduced fitness.
- Yangyang Shao
- , Ning Lu
- & Zhongjun Qin
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Letter |
53BP1–RIF1–shieldin counteracts DSB resection through CST- and Polα-dependent fill-in
53BP1 and shieldin recruit the CTC1–STN1–TEN1 complex and polymerase-α to sites of DNA damage to help control the repair of double-strand breaks.
- Zachary Mirman
- , Francisca Lottersberger
- & Titia de Lange
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Article |
Nuclear F-actin and myosins drive relocalization of heterochromatic breaks
Relocalization of heterochromatic double-strand breaks to the nuclear periphery in Drosophila cells occurs via directed motions driven by nuclear actin filaments and myosins activated by the Smc5/6 complex.
- Christopher P. Caridi
- , Carla D’Agostino
- & Irene Chiolo
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Chromosomal instability drives metastasis through a cytosolic DNA response
In chromosomally unstable tumour cells, rupture of micronuclei exposes genomic DNA and activates the cGAS–STING cytosolic DNA-sensing pathway, thereby promoting metastasis.
- Samuel F. Bakhoum
- , Bryan Ngo
- & Lewis C. Cantley
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Letter |
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN
CYREN is a direct inhibitor of classical non-homologous end joining that promotes error-free repair by homologous recombination during the S and G2 phases of the cell cycle.
- Nausica Arnoult
- , Adriana Correia
- & Jan Karlseder
The variation and evolution of complete human centromeres