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EMBO J 2021 Apr 1;40(7):e106812. Epub 2021 Mar 1.

Laboratory of Chromosome Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. Read More

J Cell Biol 2021 Mar;220(3)

Department of Biochemistry, University of Oxford, Oxford, UK.

Human centromeres form primarily on α-satellite DNA but sporadically arise de novo at naive ectopic loci, creating neocentromeres. Centromere inheritance is driven primarily by chromatin containing the histone H3 variant CENP-A. Here, we report a chromosome engineering system for neocentromere formation in human cells and characterize the first experimentally induced human neocentromere at a naive locus. Read More

Biosci Rep 2021 Jan;41(1)

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, People's Republic of China.

Breast cancer is the most common form of cancer afflicting women worldwide. Patients with breast cancer of different molecular classifications need varied treatments. Since it is known that the development of breast cancer involves multiple genes and functions, identification of functional gene modules (clusters of the functionally related genes) is indispensable as opposed to isolated genes, in order to investigate their relationship derived from the gene co-expression analysis. Read More

PLoS Genet 2020 11 11;16(11):e1008968. Epub 2020 Nov 11.

Kyoto University, Graduate School of Biostudies, Japan.

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Read More

Aging (Albany NY) 2020 11 2;12(21):22220-22232. Epub 2020 Nov 2.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.

Aneuploidy of meiotic origin is a major contributor to age-related subfertility and an increased risk of miscarriage in women. Although age-related aneuploidy has been studied in rodents, the mare may be a more appropriate animal model to study reproductive aging. Similar to women, aged mares show reduced fertility and an increased incidence of early pregnancy loss; however, it is not known whether aging predisposes to aneuploidy in equine oocytes. Read More

J Exp Bot 2021 Feb;72(4):1046-1058

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

In human cells, Haspin-mediated histone H3 threonine 3 (H3T3) phosphorylation promotes centromeric localization of the chromosomal passenger complex, thereby ensuring proper kinetochore-microtubule attachment. Haspin also binds to PDS5 cohesin-associated factor B (Pds5B), antagonizing the Wings apart-like protein homolog (Wapl)-Pds5B interaction and thus preventing Wapl from releasing centromeric cohesion during mitosis. However, the role of Haspin in plant chromosome segregation is not well understood. Read More

Comp Cytogenet 2020 9;14(4):453-482. Epub 2020 Oct 9.

Institute of Cytology and Genetics, SB RAS, pr. Lavrentyeva 10, Novosibirsk 630090, Russian Federation Institute of Cytology and Genetics Novosibirsk Russia.

The assembly of the microtubule-based spindle structure in plant meiosis remains poorly understood compared with our knowledge of mitotic spindle formation. One of the approaches in our understanding of microtubule dynamics is to study spindle assembly in meiosis of amphyhaploids. Using immunostaining with phH3Ser10, CENH3 and α-tubulin-specific antibodies, we studied the chromosome distribution and spindle organisation in meiosis of F 2R(2D)xR wheat-rye hybrids (genome structure ABDR, 4× = 28), as well as in wheat and rye mitosis and meiosis. Read More

PLoS Genet 2020 10 1;16(10):e1008928. Epub 2020 Oct 1.

Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland.

Regular chromosome segregation during the first meiotic division requires prior pairing of homologous chromosomes into bivalents. During canonical meiosis, linkage between homologous chromosomes is maintained until late metaphase I by chiasmata resulting from meiotic recombination in combination with distal sister chromatid cohesion. Separase-mediated elimination of cohesin from chromosome arms at the end of metaphase I permits terminalization of chiasmata and homolog segregation to opposite spindle poles during anaphase I. Read More

Front Genet 2020 22;11:782. Epub 2020 Jul 22.

Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by vascular cell proliferation; the pathogenesis of PAH has yet to be fully elucidated. Publicly available genetic data were downloaded from the Gene Expression Omnibus (GEO) database, and gene set enrichment analysis (GSEA) was used to determine significant differences in gene expression between tissues with PAH and healthy lung tissues. Differentially expressed genes (DEGs) were identified using the online tool, GEO2R, and functional annotation of DEGs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Read More

Essays Biochem 2020 09;64(2):251-261

Waksman Institute and Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, United States of America.

While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Read More

Am J Med Genet A 2020 11 11;182(11):2793-2796. Epub 2020 Aug 11.

Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.

Roberts syndrome (also known as Roberts-SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre- and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss-of-function variants in ESCO2, which codes for establishment of sister chromatid cohesion N-acetyltransferase 2, cause Roberts syndrome. Phenotypic spectrum among patients is broad, challenging clinical diagnosis in mildly affected individuals. Read More

PLoS Genet 2020 08 4;16(8):e1008962. Epub 2020 Aug 4.

Institut de Biologia Molecular de Barcelona, IBMB-CSIC, Barcelona, Spain.

Haspin, a highly conserved kinase in eukaryotes, has been shown to be responsible for phosphorylation of histone H3 at threonine 3 (H3T3ph) during mitosis, in mammals and yeast. Here we report that haspin is the kinase that phosphorylates H3T3 in Drosophila melanogaster and it is involved in sister chromatid cohesion during mitosis. Our data reveal that haspin also phosphorylates H3T3 in interphase. Read More

Autophagy 2021 Mar 23;17(3):796-813. Epub 2020 Jun 23.

Metabolism and Cancer Laboratory, Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.

Lysosomes, as primary degradative organelles, are the endpoint of different converging pathways, including macroautophagy. To date, lysosome degradative function has been mainly studied in interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal instability, a hallmark of cancer. Read More

Essays Biochem 2020 09;64(2):289-297

Department of Biochemistry and Molecular Biology, Tulane University Health Science Center, 1430 Tulane Ave, New Orleans LA 70112, U.S.A.

Proper regulation of centromeric cohesion is required for faithful chromosome segregation that prevents chromosomal instability. Extensive studies have identified and established the conserved protein Shugoshin (Sgo1/2) as an essential protector for centromeric cohesion. In this review, we summarize the current understanding of how Shugoshin-1 (Sgo1) protects centromeric cohesion at the molecular level. Read More

Genome Med 2020 04 28;12(1):38. Epub 2020 Apr 28.

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Background: Pancreatic neuroendocrine tumors (PANETs) are rare, slow growing cancers that often present with local and distant metastasis upon detection. PANETS contain distinct karyotypes, epigenetic dysregulation, and recurrent mutations in MEN1, ATRX, and DAXX (MAD+); however, the molecular basis of disease progression remains uncharacterized.

Methods: We evaluated associations between aneuploidy and the MAD+ mutational state of 532 PANETs from 11 published genomic studies and 19 new cases using a combination of exome, targeted panel, shallow WGS, or RNA-seq. Read More

Blood 2020 07;136(3):313-327

Josep Carreras Leukemia Research Institute, Barcelona, Spain.

B-cell acute lymphoblastic leukemia (ALL; B-ALL) is the most common pediatric cancer, and high hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD being an initiating oncogenic event affiliated with childhood B-ALL, the mitotic and chromosomal defects associated with HyperD B-ALL (HyperD-ALL) remain poorly characterized. Here, we have used 54 primary pediatric B-ALL samples to characterize the cellular-molecular mechanisms underlying the mitotic/chromosome defects predicated to be early pathogenic contributors in HyperD-ALL. Read More

F1000Res 2020 28;9. Epub 2020 Jan 28.

CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.

The goal of mitosis is to form two daughter cells each containing one copy of each mother cell chromosome, replicated in the previous S phase. To achieve this, sister chromatids held together back-to-back at their primary constriction, the centromere, have to interact with microtubules of the mitotic spindle so that each chromatid takes connections with microtubules emanating from opposite spindle poles (we will refer to this condition as bipolar attachment). Only once all replicated chromosomes have reached bipolar attachments can sister chromatids lose cohesion with each other, at the onset of anaphase, and move toward opposite spindle poles, being segregated into what will soon become the daughter cell nucleus. Read More

Exp Cell Res 2020 04 8;389(2):111900. Epub 2020 Feb 8.

Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, 292-0818, Japan. Electronic address:

The centromere is a specialized chromosomal locus required for accurate chromosome segregation. Heterochromatin also assembles around centromere chromatin and forms a base that supports sister chromatid cohesion until anaphase begins. Both centromere chromatin and heterochromatin assemble on a centromeric DNA sequence, a highly repetitive sequence called alphoid DNA (α-satellite DNA) in humans. Read More

Mol Cell 2020 03 6;77(6):1279-1293.e4. Epub 2020 Feb 6.

Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31000 Toulouse, France. Electronic address:

Cohesin, a member of the SMC complex family, holds sister chromatids together but also shapes chromosomes by promoting the formation of long-range intra-chromatid loops, a process proposed to be mediated by DNA loop extrusion. Here we describe the roles of three cohesin partners, Pds5, Wpl1, and Eco1, in loop formation along either unreplicated or mitotic Saccharomyces cerevisiae chromosomes. Pds5 limits the size of DNA loops via two different pathways: the canonical Wpl1-mediated releasing activity and an Eco1-dependent mechanism. Read More

Curr Biol 2020 02 30;30(4):715-722.e3. Epub 2020 Jan 30.

Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address:

Polo-like kinases (PLKs) have numerous roles in both mitosis and meiosis, including functions related to chromosome segregation, cohesin removal, and kinetochore orientation [1-7]. PLKs require specific regulation during meiosis to control those processes. Genetic studies demonstrate that the Drosophila PLK Polo kinase (Polo) is inhibited by the female meiosis-specific protein Matrimony (Mtrm) in a stoichiometric manner [8]. Read More

Front Cell Dev Biol 2019 10;7:343. Epub 2020 Jan 10.

Institute of Biochemistry II, Medical Faculty, Goethe University, Frankfurt, Germany.

The dynamic and reversible post-translational modification of proteins and protein complexes with the ubiquitin-related SUMO modifier regulates a wide variety of nuclear functions, such as transcription, replication and DNA repair. SUMO can be attached as a monomer to its targets, but can also form polymeric SUMO chains. While monoSUMOylation is generally involved in the assembly of protein complexes, multi- or polySUMOylation may have very different consequences. Read More

Plant Cell 2020 04 29;32(4):1323-1336. Epub 2020 Jan 29.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China

Meiosis consists of two highly conserved nuclear divisions, which allow eukaryotes to maintain their chromosome number through sexual reproduction. The successful completion of meiosis depends on homologous chromosome pairing. Centromere interactions during early meiotic prophase I facilitate homologous chromosome pairing, but the underlying mechanism is unclear. Read More

Curr Biol 2019 11 31;29(22):3749-3765.e7. Epub 2019 Oct 31.

Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany. Electronic address:

Chromosome segregation errors during female meiosis are a leading cause of pregnancy loss and human infertility. The segregation of chromosomes is driven by interactions between spindle microtubules and kinetochores. Kinetochores in mammalian oocytes are subjected to special challenges: they need to withstand microtubule pulling forces over multiple hours and are built on centromeric chromatin that in humans is decades old. Read More

BMC Mol Cell Biol 2019 10 22;20(1):44. Epub 2019 Oct 22.

Department of Bio-sciences and Bio-engineering, IIT Bombay, Mumbai, India.

Background: Meiosis-I is a unique type of chromosome segregation where each chromosome aligns and segregates from its homolog. The mechanism of meiosis I homolog separation in different eukaryotes depends on their centromere and kinetochore architecture which in turn relies mainly on two processes, first on a specialized four protein complex known as monopolin and second, the centromeric cohesion protection (CCP). However, in mammals the complex has not been identified. Read More

Nat Commun 2019 09 17;10(1):4224. Epub 2019 Sep 17.

Children's Medical Research Institute, University of Sydney, Westmead, NSW, 2145, Australia.

Mitotic catastrophe is a broad descriptor encompassing unclear mechanisms of cell death. Here we investigate replication stress-driven mitotic catastrophe in human cells and identify that replication stress principally induces mitotic death signalled through two independent pathways. In p53-compromised cells we find that lethal replication stress confers WAPL-dependent centromere cohesion defects that maintain spindle assembly checkpoint-dependent mitotic arrest in the same cell cycle. Read More

Nat Cell Biol 2019 09 3;21(9):1127-1137. Epub 2019 Sep 3.

Department of Cell Biology, University of Virginia, School of Medicine, Charlottesville, VA, USA.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. Read More

Cell Cycle 2019 Oct 6;18(19):2481-2494. Epub 2019 Aug 6.

College of Animal Science and Technology, Nanjing Agricultural University , Nanjing , China.

In mammalian cells, cohesin acetyltransferases Esco1 and Esco2 acetylate cohesin subunit Smc3 to establish chromosome cohesion, ensuring the accurate chromosome segregation. However, we have previously documented that both Esco1 and Esco2 have unique substrates and roles in mouse oocyte meiosis I to orchestrate the meiotic progression, but whether these functions are conserved among species is still not determined. Here, we used porcine oocytes as a model to illustrate that Esco1 and Esco2 exerted conserved functions during oocyte meiosis. Read More

Proc Natl Acad Sci U S A 2019 08 24;116(32):15967-15972. Epub 2019 Jul 24.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China;

The organization of microtubules into a bipolar spindle is essential for chromosome segregation. Both centrosome and chromatin-dependent spindle assembly mechanisms are well studied in mouse, , and oocytes; however, the mechanism of bipolar spindle assembly in plant meiosis remains elusive. According to our observations of microtubule assembly in , , , and , we propose that a key step of plant bipolar spindle assembly is the correction of the multipolar spindle into a bipolar spindle at metaphase I. Read More

J Cell Biol 2019 08 21;218(8):2514-2528. Epub 2019 Jun 21.

Department of Biochemistry and Molecular Biology and Tulane Aging Center, Tulane University Health Science Center, New Orleans, LA

At anaphase onset, Sgo1 function of cohesion protection must be disabled to allow timely chromosome segregation, but how this is achieved is not fully understood. Here, we show that SET, a known PP2A inhibitor, directly binds to a domain in Sgo1 in close proximity to the cohesin-binding motif. The Sgo1-cohesin binding can be disrupted by SET in a dose-dependent manner in vitro as well as by SET overexpression in cells, suggesting that SET is also an inhibitor to the Sgo1-cohesin binding. Read More

Genes (Basel) 2019 06 20;10(6). Epub 2019 Jun 20.

Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Via Ferrata 1, 27100 Pavia, Italy.

The typical vertebrate centromeres contain long stretches of highly repeated DNA sequences (satellite DNA). We previously demonstrated that the karyotypes of the species belonging to the genus are characterized by the presence of satellite-free and satellite-based centromeres and represent a unique biological model for the study of centromere organization and behavior. Using horse primary fibroblasts cultured in vitro, we compared the segregation fidelity of chromosome 11, whose centromere is satellite-free, with that of chromosome 13, which has similar size and a centromere containing long stretches of satellite DNA. Read More