Centromeres

  • 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

    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

    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

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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 |

    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
    | Open Access

    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
    | Open Access

    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