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| Open AccessConserved chromatin and repetitive patterns reveal slow genome evolution in frogs
Frogs are an ancient and ecologically diverse group of amphibians that include important model systems. This paper reports genome sequences of multiple frog species, revealing remarkable stability of frog chromosomes and centromeres, along with highly recombinogenic extended subtelomeres.
- Jessen V. Bredeson
- , Austin B. Mudd
- & Daniel S. Rokhsar
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Article
| Open AccessCENP-A and CENP-B collaborate to create an open centromeric chromatin state
Centromeres are defined by the histone variant CENP-A. Using single-molecule fluorescence and cryoEM, this study shows that CENP-A and the centromeric protein CENP-B collaborate to create dynamic and open chromatin, aiding centromeric factor binding.
- Harsh Nagpal
- , Ahmad Ali-Ahmad
- & Beat Fierz
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Article
| Open AccessDefining a core configuration for human centromeres during mitosis
The detailed 3D organization of human centromere components is unknown. Here, the authors use super-resolution microscopy to present a working model for a common core centromere structure.
- Ayantika Sen Gupta
- , Chris Seidel
- & Jennifer L. Gerton
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Article
| Open AccessRio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores
Kinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of centromere transcripts (cenRNAs). Here the authors show the Rio1 kinase limits cenRNA production by reducing RNAPII accessibility and promotes cenRNA degradation by the 5’− 3’exoribonuclease Rat1.
- Ksenia Smurova
- , Michela Damizia
- & Peter De Wulf
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Article
| Open AccessCentromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis
Fibrosis of the skin plays an important role in scleroderma. Here the authors demonstrate genetic and epigenetic abnormalities at the centromere that affect the replication of the chromosomes, resulting in activation of pathways involved in inflammation and fibrosis
- Souren Paul
- , Mark H. Kaplan
- & Rafael Contreras-Galindo
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Article
| Open AccessHuman centromere repositioning activates transcription and opens chromatin fibre structure
In this study, using a human neocentromere as a model, the authors show that centromeres have a special chromatin structure. Centromere repositioning triggers transcriptional activation, epigenetic remodelling and chromatin fibre decompaction.
- Catherine Naughton
- , Covadonga Huidobro
- & Nick Gilbert
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Article
| Open AccessRecruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions
The kinetochores contain multiple protein interaction networks. Takenoshita et al. analyzed the complicated networks using the genetic method and revealed that two copies of Ndc80 complexes on CENP-T are sufficient for kinetochore functions.
- Yusuke Takenoshita
- , Masatoshi Hara
- & Tatsuo Fukagawa
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Article
| Open AccessA compendium of chromatin contact maps reflecting regulation by chromatin remodelers in budding yeast
The effect of ATP-dependent chromatin remodelers on 3D genome organization has not been well studied. Here the authors employ in situ Hi-C with an auxin-inducible degron system to degrade chromatin remodelers in yeast to find that the 3D structure of chromatin collapses in their absence. The chromatin remodeling can modulate 3D architecture depending on chromosomal context and cell cycle stage.
- Hyelim Jo
- , Taemook Kim
- & Daeyoup Lee
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Article
| Open AccessHelicase LSH/Hells regulates kinetochore function, histone H3/Thr3 phosphorylation and centromere transcription during oocyte meiosis
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
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Article
| Open AccessSpt6 is a maintenance factor for centromeric CENP-A
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
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Article
| Open AccessGenetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin
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
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Article
| Open AccessCENP-A nucleosome clusters form rosette-like structures around HJURP during G1
Human centromeric nucleosomes contain the specific CENP-A histone variant, which replaces canonical histone H3 and epigenetically marks the centromeres. Here the authors show that CENP-A nucleosomes form large supramolecular clusters during the G1 phase of the cell cycle which are arranged as rosette-like structures.
- Leonid Andronov
- , Khalid Ouararhni
- & Ali Hamiche
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Article
| Open AccessMechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
The CENP-A chaperone HJURP associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. Here the authors provide evidence that two repeats in human HJURP previously proposed to be functionally distinct are interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it.
- Dongqing Pan
- , Kai Walstein
- & Andrea Musacchio
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Article
| Open AccessThe poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation
While the biological roles of ubiquitin chains are well studied, little is known about the functions of SUMO polymers. Here, the authors identify poly-SUMOylation substrates and provide evidence that SUMO polymers regulate the accumulation of CCAN subunits at chromatin and centromeres.
- Frauke Liebelt
- , Nicolette S. Jansen
- & Alfred C. O. Vertegaal
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Article
| Open AccessPLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling
The kinase PLK1 has important roles during cell division, including mitotic entry and bipolar spindle formation. Here, the authors show that PLK1 also functions in centromere protection, with loss leading to DNA unwinding by Bloom’s syndrome helicase and subsequent collapse of chromosome alignment.
- Owen Addis Jones
- , Ankana Tiwari
- & Kok-Lung Chan
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Article
| Open AccessInterspecies conservation of organisation and function between nonhomologous regional centromeres
Although the centromere-specific histone CENP-A usually assembles on specific genomic sequences, centromeric DNA is not conserved. Here the authors characterize the genome and centromeres of related fission yeasts and provide evidence that Schizosaccharomyces centromere DNA possesses intrinsic conserved properties that promote assembly of CENP-A chromatin.
- Pin Tong
- , Alison L. Pidoux
- & Robin C. Allshire
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Article
| Open AccessAtomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment
CENP-A histone variants replace histones H3 at centromeres. Here the authors use a single-chain antibody fragment (scFv) to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by cryo-EM to 2.6 Å resolution, providing insight into the structure and function of the CENP-A nucleosome.
- Bing-Rui Zhou
- , K. N. Sathish Yadav
- & Ping Zhang
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Article
| Open AccessPhosphorylation of CENP-A on serine 7 does not control centromere function
Phosphorylation of CENP-A on serine 7 has been proposed to control centromere assembly and function. Here, the authors use gene targeting at both endogenous CENP-A alleles and gene replacement in human cells to demonstrate that CENP-A that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability.
- Viviana Barra
- , Glennis A. Logsdon
- & Daniele Fachinetti
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Review Article
| Open AccessThe dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA
Centromeres are the chromosomal domains that regulate assembly of the components required for chromosome separation. Here the authors review how centromeres are a potential source of genome instability and link centromere aberrations and rearrangements to human diseases such as cancer.
- V. Barra
- & D. Fachinetti
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Article
| Open AccessSpindle tubulin and MTOC asymmetries may explain meiotic drive in oocytes
During ‘meiotic drive’, some chromosomes can bias their spindle orientation and thus be retained in the egg. Here, the authors find that this phenomenon can be driven by microtubule force asymmetry on chromosomes with differently sized centromeres and kinetochores.
- Tianyu Wu
- , Simon I. R. Lane
- & Keith T. Jones
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Article
| Open AccessATP synthase F1 subunits recruited to centromeres by CENP-A are required for male meiosis
The histone H3 CENP-A is known to play a role during meiosis but its role in the testes in the fly is unknown. Here, the authors identify the mitochondrial metabolic protein complex ATP synthase F1 as interacting with CENP-A, promoting centromere cohesion during meiosis and affecting fly fertility.
- Caitríona M. Collins
- , Beatrice Malacrida
- & Elaine M. Dunleavy
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Article
| Open AccessAurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue
Sustained spindle tension applied to sister centromeres during mitosis leads to loss of sister chromatid cohesion which is known as cohesion fatigue. Here the authors show that Aurora A-dependent phosphorylation of CENP-A at the inner centromeres protects bioriented chromosomes against cohesion fatigue.
- Grégory Eot-Houllier
- , Laura Magnaghi-Jaulin
- & Christian Jaulin
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Article
| Open Access53BP1 can limit sister-chromatid rupture and rearrangements driven by a distinct ultrafine DNA bridging-breakage process
Chromosome instability is associated with cancer formation. Here the authors identify in cultured human cancer cells a non-canonical DNA bridge breakage pathway leading to chromosome missegregation and rearrangements triggered by sister DNA intertwinements, which are limited by 53BP1.
- Ankana Tiwari
- , Owen Addis Jones
- & Kok-Lung Chan
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Article
| Open AccessThe Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3
The histone variant CENP-A marks active centromeres and replaces H3 at centromeres through a poorly understood mechanism. Here, the authors provide evidence that the chromatin remodeller Ino80 promotes CENP-A chromatin assembly at the centromere in fission yeast.
- Eun Shik Choi
- , Youngseo Cheon
- & Daeyoup Lee
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Article
| Open AccessCentromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition
Centromere maintenance depends on the persistence of the histone variant CENP-A at the centromeres. Here, the authors characterize the core centromeric nucleosome complex wherein CENP-C confers a stable CENP-A nucleosome conformation and CENP-N fastens CENP-A to the DNA.
- Lucie Y. Guo
- , Praveen Kumar Allu
- & Ben E. Black
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Article
| Open AccessInner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing
Precise chromosome segregation during mitosis requires coordination of stable chromosome bi-orientation with anaphase onset, however the underlying mechanism is not clear. Here the authors show that inner centromere localization of the chromosomal passenger complex maintains centromeric cohesion on bi-oriented chromosomes and allows mitotic checkpoint silencing.
- Rutger C. C. Hengeveld
- , Martijn J. M. Vromans
- & Susanne M. A. Lens
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Article
| Open Accessα-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere
Centromeres are chromosomal domains epigenetically specified by the presence of the CENP-A containing nucleosomes that control chromosome segregation. Here the authors show that α-amino trimethylation of CENP-A by the enzyme NRMT is required for centromere function, faithful chromosome segregation and cell survival.
- Kizhakke M. Sathyan
- , Daniele Fachinetti
- & Daniel R. Foltz
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Article
| Open AccessEpigenetic engineering reveals a balance between histone modifications and transcription in kinetochore maintenance
Centromeres are centrochromatin domains with CENP-A and H3 nucleosomes carrying transcription-associated modifications. Here the authors target synthetic modules to the centromeres to show that transcription plus histone modifications are required for CENP-A assembly and centrochromatin maintenance.
- Oscar Molina
- , Giulia Vargiu
- & William C. Earnshaw
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Article
| Open AccessAcetylation of histone H4 lysine 5 and 12 is required for CENP-A deposition into centromeres
The deposition of histone H3 variant CENP-A bound with histone H4 is a key feature designating the centromere region of a chromosome. Here the authors show acetylation on residues K5 and K12 in histone H4, mediated by the RbAp46/48-Hat1 complex, is required for deposition of CENP-A-H4 into centromeres.
- Wei-Hao Shang
- , Tetsuya Hori
- & Tatsuo Fukagawa
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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
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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
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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
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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
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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