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https://www.readbyqxmd.com/read/28514186/apc-c-cdc20-mediates-deprotection-of-centromeric-cohesin-at-meiosis-ii-in-yeast
#1
Katarzyna Jonak, Ievgeniia Zagoriy, Tugce Oz, Peter Graf, Julie Rojas, Valentina Mengoli, Wolfgang Zachariae
Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage...
May 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28502659/apc-c-cdh1-enables-removal-of-shugoshin-2-from-the-arms-of-bivalent-chromosomes-by-moderating-cyclin-dependent-kinase-activity
#2
Ahmed Rattani, Randy Ballesteros Mejia, Katherine Roberts, Maurici B Roig, Jonathan Godwin, Michael Hopkins, Manuel Eguren, Luis Sanchez-Pulido, Elwy Okaz, Sugako Ogushi, Magda Wolna, Jean Metson, Alberto M Pendás, Marcos Malumbres, Béla Novák, Mary Herbert, Kim Nasmyth
In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/C(Cdc20)) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28497540/meikin-associated-polo-like-kinase-specifies-bub1-distribution-in-meiosis-i
#3
Seira Miyazaki, Jihye Kim, Yuya Yamagishi, Tadashi Ishiguro, Yuki Okada, Yuji Tanno, Takeshi Sakuno, Yoshinori Watanabe
In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1...
May 12, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#4
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28483814/dalmatian-spotting-the-difference-in-cohesin-protectors
#5
Adele L Marston
The cohesin complex prevents separation of chromosomes following their duplication until the appropriate time during cell division. In vertebrates, establishment and maintenance of cohesin-dependent linkages depend on two distinct proteins, sororin and shugoshin. New findings published in The EMBO Journal show that in Drosophila, the function of both of these cohesin regulators is carried out by a single hybrid protein, Dalmatian.
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28017619/casein-kinase-1-coordinates-cohesin-cleavage-gametogenesis-and-exit-from-m-phase-in-meiosis-ii
#6
Orlando Argüello-Miranda, Ievgeniia Zagoriy, Valentina Mengoli, Julie Rojas, Katarzyna Jonak, Tugce Oz, Peter Graf, Wolfgang Zachariae
Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28007967/aberrant-meiotic-modulation-partially-contributes-to-the-lower-germination-rate-of-pollen-grains-in-maize-zea-mays-l-under-low-nitrogen-supply
#7
Hongyan Zheng, Huamao Wu, Xiaoying Pan, Weiwei Jin, Xuexian Li
Pollen germination is an essential step towards successful pollination during maize reproduction. How low niutrogen (N) affects pollen germination remains an interesting biological question to be addressed. We found that only low N resulted in a significantly lower germination rate of pollen grains after 4 weeks of low N, phosphorus or potassium treatment in maize production. Importantly, cytological analysis showed 7-fold more micronuclei in male meiocytes under the low N treatment than in the control, indicating that the lower germination rate of pollen grains was partially due to numerous chromosome loss events resulting from preceding meiosis...
November 15, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27917322/bioinformatical-analysis-of-eukaryotic-shugoshins-reveals-meiosis-specific-features-of-vertebrate-shugoshins
#8
Tatiana M Grishaeva, Darya Kulichenko, Yuri F Bogdanov
BACKGROUND: Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms. METHODS: A bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed...
2016: PeerJ
https://www.readbyqxmd.com/read/27672091/identification-of-tension-sensing-motif-of-histone-h3-in-saccharomyces-cerevisiae-and-its-regulation-by-histone-modifying-enzymes
#9
Jianjun Luo, Xiexiong Deng, Christopher Buehl, Xinjing Xu, Min-Hao Kuo
To ensure genome stability during cell division, all chromosomes must attach to spindles emanating from the opposite spindle pole bodies before segregation. The tension between sister chromatids generated by the poleward pulling force is an integral part of chromosome biorientation. In budding yeast, the residue Gly44 of histone H3 is critical for retaining the conserved Shugoshin protein Sgo1p at the pericentromeres for monitoring the tension status during mitosis. Studies carried out in this work showed that Lys42, Gly44, and Thr45 of H3 form the core of a tension sensing motif (TSM)...
November 2016: Genetics
https://www.readbyqxmd.com/read/27629923/mutations-of-sgo2-and-cldn14-collectively-cause-coincidental-perrault-syndrome
#10
R Faridi, A U Rehman, R J Morell, P L Friedman, L Demain, S Zahra, A A Khan, D Tohlob, M Z Assir, G Beaman, S N Khan, W G Newman, S Riazuddin, T B Friedman
Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing...
February 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27539729/sgo1-is-involved-in-the-dna-damage-response-in-mycn-amplified-neuroblastoma-cells
#11
Yuko Murakami-Tonami, Haruna Ikeda, Ryota Yamagishi, Mao Inayoshi, Shiho Inagaki, Satoshi Kishida, Yosuke Komata, Jan Koster, Ichiro Takeuchi, Yutaka Kondo, Tohru Maeda, Yoshitaka Sekido, Hiroshi Murakami, Kenji Kadomatsu
Shugoshin 1 (SGO1) is required for accurate chromosome segregation during mitosis and meiosis; however, its other functions, especially at interphase, are not clearly understood. Here, we found that downregulation of SGO1 caused a synergistic phenotype in cells overexpressing MYCN. Downregulation of SGO1 impaired proliferation and induced DNA damage followed by a senescence-like phenotype only in MYCN-overexpressing neuroblastoma cells. In these cells, SGO1 knockdown induced DNA damage, even during interphase, and this effect was independent of cohesin...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27526110/systemic-chromosome-instability-in-shugoshin-1-mice-resulted-in-compromised-glutathione-pathway-activation-of-wnt-signaling-and-defects-in-immune-system-in-the-lung
#12
H Y Yamada, G Kumar, Y Zhang, E Rubin, S Lightfoot, W Dai, C V Rao
Mitotic error-mediated chromosome instability (CIN) can lead to aneuploidy, chromothripsis, DNA damage and/or whole chromosome gain/loss. CIN may prompt rapid accumulation of mutations and genomic alterations. Thus, CIN can promote carcinogenesis. This CIN process results from a mutation in certain genes or environmental challenge such as smoking, and is highly prevalent in various cancers, including lung cancer. A better understanding of the effects of CIN on carcinogenesis will lead to novel methods for cancer prevention and treatment...
August 15, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27350047/crystal-structure-of-a-pp2a-b56-bubr1-complex-and-its-implications-for-pp2a-substrate-recruitment-and-localization
#13
Jiao Wang, Zhizhi Wang, Tingting Yu, Huan Yang, David M Virshup, Geert J P L Kops, Sang Hyun Lee, Weihong Zhou, Xin Li, Wenqing Xu, Zihe Rao
Protein phosphatase 2A (PP2A) accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kinetochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1...
July 2016: Protein & Cell
https://www.readbyqxmd.com/read/27116032/bub1-targeting-to-centromeres-is-sufficient-for-sgo1-recruitment-in-the-absence-of-kinetochores
#14
Samantha J Williams, Ariane Abrieu, Ana Losada
Centromeric chromatin containing the histone H3 variant centromere protein A (CENP-A) directs kinetochore assembly through a hierarchical binding of CENPs, starting with CENP-C and CENP-T. Centromeres are also the chromosomal regions where cohesion, mediated by cohesin, is most prominently maintained in mitosis. While most cohesin dissociates from chromosome arms in prophase, Shugoshin 1 (Sgo1) prevents this process at centromeres. Centromeric localization of Sgo1 depends on histone H2A phosphorylation by the kinase Bub1, but whether additional interactions with kinetochore components are required for Sgo1 recruitment is unclear...
March 2017: Chromosoma
https://www.readbyqxmd.com/read/26998746/condensin-in-chromatid-cohesion-and-segregation
#15
REVIEW
Susumu Uchiyama, Kiichi Fukui
After replication of genomic DNA during the S phase, 2 chromatids hold together longitudinally. When cells enter mitosis, the paired sister chromatids start to condense and then segregate into individual chromatids except for the centromeric region. Upon attachment of microtubules to the kinetochore, subsequent pulling of the 2 sister chromatids by the spindles towards opposite poles results in 2 completely separated chromatids. Besides more than 100 kinds of kinetochore proteins, several key proteins such as cohesin, separase, shugoshin, and condensin contribute to chromatid cohesion and segregation...
2015: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/26934308/insights-into-centromeric-transcription-in-mitosis
#16
Hong Liu
The major role of RNA polymerase II (RNAP II) is to generate mRNAs. I recently uncovered a novel function of RNAP II in chromosome segregation in mitosis, installing the cohesin protector, Shugoshin, at centromeres. Here I will discuss the current understanding of RNAP II-dependent centromeric transcription in mitosis.
2016: Transcription
https://www.readbyqxmd.com/read/26885717/probing-the-catalytic-functions-of-bub1-kinase-using-the-small-molecule-inhibitors-bay-320-and-bay-524
#17
Anna P Baron, Conrad von Schubert, Fabien Cubizolles, Gerhard Siemeister, Marion Hitchcock, Anne Mengel, Jens Schröder, Amaury Fernández-Montalván, Franz von Nussbaum, Dominik Mumberg, Erich A Nigg
The kinase Bub1 functions in the spindle assembly checkpoint (SAC) and in chromosome congression, but the role of its catalytic activity remains controversial. Here, we use two novel Bub1 inhibitors, BAY-320 and BAY-524, to demonstrate potent Bub1 kinase inhibition both in vitro and in intact cells. Then, we compared the cellular phenotypes of Bub1 kinase inhibition in HeLa and RPE1 cells with those of protein depletion, indicative of catalytic or scaffolding functions, respectively. Bub1 inhibition affected chromosome association of Shugoshin and the chromosomal passenger complex (CPC), without abolishing global Aurora B function...
February 17, 2016: ELife
https://www.readbyqxmd.com/read/26833665/systemic-chromosome-instability-resulted-in-colonic-transcriptomic-changes-in-metabolic-proliferation-and-stem-cell-regulators-in-sgo1-mice
#18
Chinthalapally V Rao, Saira Sanghera, Yuting Zhang, Laura Biddick, Arun Reddy, Stan Lightfoot, Naveena B Janakiram, Altaf Mohammed, Wei Dai, Hiroshi Y Yamada
Colon cancer is the second most lethal cancer and is predicted to claim 49,700 lives in the United States this year. Chromosome instability (CIN) is observed in 80% to 90% of colon cancers and is thought to contribute to colon cancer progression and recurrence. To investigate the impact of CIN on colon cancer development, we developed shugoshin-1 (Sgo1) haploinsufficient (-/+) mice, an animal model focusing on mitotic error-induced CIN. In this study, we analyzed signature changes in the colonic transcriptome of Sgo1(-/+) mice to examine the molecular events underlying the altered carcinogenesis profiles in Sgo1(-/+) mice...
February 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/26804021/shugoshin-forms-a-specialized-chromatin-domain-at-subtelomeres-that-regulates-transcription-and-replication-timing
#19
Sanki Tashiro, Tetsuya Handa, Atsushi Matsuda, Takuto Ban, Toru Takigawa, Kazumi Miyasato, Kojiro Ishii, Kazuto Kugou, Kunihiro Ohta, Yasushi Hiraoka, Hisao Masukata, Junko Kanoh
A chromosome is composed of structurally and functionally distinct domains. However, the molecular mechanisms underlying the formation of chromatin structure and the function of subtelomeres, the telomere-adjacent regions, remain obscure. Here we report the roles of the conserved centromeric protein Shugoshin 2 (Sgo2) in defining chromatin structure and functions of the subtelomeres in the fission yeast Schizosaccharomyces pombe. We show that Sgo2 localizes at the subtelomeres preferentially during G2 phase and is essential for the formation of a highly condensed subtelomeric chromatin body 'knob'...
2016: Nature Communications
https://www.readbyqxmd.com/read/26506018/sgo1c-is-a-non-functional-isoform-of-shugoshin-and-can-disrupt-sister-chromatid-cohesion-by-interacting-with-pp2a-b56
#20
Wing Ki Wong, Terrenz Kelly, Jingjing Li, Hoi Tang Ma, Randy Y C Poon
Shugoshin (SGO1) plays a pivotal role in sister chromatid cohesion during mitosis by protecting the centromeric cohesin from mitotic kinases and WAPL. Mammalian cells contain at least 6 alternatively spliced isoforms of SGO1. The relationship between the canonical SGO1A with shorter isoforms including SGO1C remains obscure. Here we show that SGO1C was unable to replace the loss of SGO1A. Instead, expression of SGO1C alone induced aberrant mitosis similar to depletion of SGO1A, promoting premature sister chromatid separation, activation of the spindle-assembly checkpoint, and mitotic arrest...
2015: Cell Cycle
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