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https://www.readbyqxmd.com/read/28220956/releasing-the-cohesin-ring-a-rigid-scaffold-model-for-opening-the-dna-exit-gate-by-pds5-and-wapl
#1
Zhuqing Ouyang, Hongtao Yu
The ring-shaped ATPase machine, cohesin, regulates sister chromatid cohesion, transcription, and DNA repair by topologically entrapping DNA. Here, we propose a rigid scaffold model to explain how the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Recent studies have established the Smc3-Scc1 interface as the DNA exit gate of cohesin, revealed a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28210885/cohesin-biology-meets-the-loop-extrusion-model
#2
REVIEW
Christopher Barrington, Ronald Finn, Suzana Hadjur
Extensive research has revealed that cohesin acts as a topological device, trapping chromosomal DNA within a large tripartite ring. In so doing, cohesin contributes to the formation of compact and organized genomes. How exactly the cohesin subunits interact, how it opens, closes, and translocates on chromatin, and how it actually tethers DNA strands together are still being elucidated. A comprehensive understanding of these questions will shed light on how cohesin performs its many functions, including its recently proposed role as a chromatid loop extruder...
February 16, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28199302/untimely-expression-of-gametogenic-genes-in-vegetative-cells-causes-uniparental-disomy
#3
H Diego Folco, Venkata R Chalamcharla, Tomoyasu Sugiyama, Gobi Thillainadesan, Martin Zofall, Vanivilasini Balachandran, Jothy Dhakshnamoorthy, Takeshi Mizuguchi, Shiv I S Grewal
Uniparental disomy (UPD), in which an individual contains a pair of homologous chromosomes originating from only one parent, is a frequent phenomenon that is linked to congenital disorders and various cancers. UPD is thought to result mostly from pre- or post-zygotic chromosome missegregation. However, the factors that drive UPD remain unknown. Here we use the fission yeast Schizosaccharomyces pombe as a model to investigate UPD, and show that defects in the RNA interference (RNAi) machinery or in the YTH domain-containing RNA elimination factor Mmi1 cause high levels of UPD in vegetative diploid cells...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28186207/complexity-of-the-ruminococcus-flavefaciens-fd-1-cellulosome-reflects-an-expansion-of-family-related-protein-protein-interactions
#4
Vered Israeli-Ruimy, Pedro Bule, Sadanari Jindou, Bareket Dassa, Sarah Moraïs, Ilya Borovok, Yoav Barak, Michal Slutzki, Yuval Hamberg, Vânia Cardoso, Victor D Alves, Shabir Najmudin, Bryan A White, Harry J Flint, Harry J Gilbert, Raphael Lamed, Carlos M G A Fontes, Edward A Bayer
Protein-protein interactions play a vital role in cellular processes as exemplified by assembly of the intricate multi-enzyme cellulosome complex. Cellulosomes are assembled by selective high-affinity binding of enzyme-borne dockerin modules to repeated cohesin modules of structural proteins termed scaffoldins. Recent sequencing of the fiber-degrading Ruminococcus flavefaciens FD-1 genome revealed a particularly elaborate cellulosome system. In total, 223 dockerin-bearing ORFs potentially involved in cellulosome assembly and a variety of multi-modular scaffoldins were identified, and the dockerins were classified into six major groups...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181049/condensin-master-organizer-of-the-genome
#5
REVIEW
Paul Kalitsis, Tao Zhang, Kathryn M Marshall, Christian F Nielsen, Damien F Hudson
A fundamental requirement in nature is for a cell to correctly package and divide its replicated genome. Condensin is a mechanical multisubunit complex critical to this process. Condensin uses ATP to power conformational changes in DNA to enable to correct DNA compaction, organization, and segregation of DNA from the simplest bacteria to humans. The highly conserved nature of the condensin complex and the structural similarities it shares with the related cohesin complex have provided important clues as to how it functions in cells...
February 9, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28178516/chromatin-states-in-mouse-sperm-correlate-with-embryonic-and-adult-regulatory-landscapes
#6
Yoon Hee Jung, Michael E G Sauria, Xiaowen Lyu, Manjinder S Cheema, Juan Ausio, James Taylor, Victor G Corces
The mammalian sperm genome is thought to lack substantial information for the regulation of future expression after fertilization. Here, we show that most promoters in mouse sperm are flanked by well-positioned nucleosomes marked by active histone modifications. Analysis of these modifications suggests that many enhancers and super-enhancers functional in embryonic and adult tissues are already specified in sperm. The sperm genome is bound by CTCF and cohesin at sites that are also present in round spermatids and embryonic stem cells (ESCs)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177203/biology-and-insights-into-the-role-of-cohesin-protease-separase-in-human-malignancies
#7
Nenggang Zhang, Debananda Pati
Separase, an enzyme that resolves sister chromatid cohesion during the metaphase-to-anaphase transition, plays a pivotal role in chromosomal segregation and cell division. Separase protein, encoded by the extra spindle pole bodies like 1 (ESPL1) gene, is overexpressed in numerous human cancers including breast, bone, brain, and prostate. Separase is oncogenic, and its overexpression is sufficient to induce mammary tumours in mice. Either acute or chronic overexpression of separase in mouse mammary glands leads to aneuploidy and tumorigenesis, and inhibition of separase enzymatic activity decreases the growth of human breast tumour xenografts in mice...
February 8, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28169291/hotspots-of-aberrant-enhancer-activity-punctuate-the-colorectal-cancer-epigenome
#8
Andrea J Cohen, Alina Saiakhova, Olivia Corradin, Jennifer M Luppino, Katreya Lovrenert, Cynthia F Bartels, James J Morrow, Stephen C Mack, Gursimran Dhillon, Lydia Beard, Lois Myeroff, Matthew F Kalady, Joseph Willis, James E Bradner, Ruth A Keri, Nathan A Berger, Shondra M Pruett-Miller, Sanford D Markowitz, Peter C Scacheri
In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28167679/independent-mechanisms-recruit-the-cohesin-loader-protein-nipbl-to-sites-of-dna-damage
#9
Christopher Bot, Annika Pfeiffer, Fosco Giordano, Dharani Manjeera Edara, Nico P Dantuma, Lena Ström
NIPBL is required to load the cohesin complex on to DNA. While the canonical role of cohesin is to couple replicated sister chromatids together until the onset of mitosis, it also promotes tolerance to DNA damage. Here we show that NIPBL is recruited to DNA damage throughout the cell cycle via independent mechanisms, influenced by type of damage. Firstly, the heterochromatin protein HP1γ recruits NIPBL to DSBs through the corresponding HP1-binding motif within the N-terminus. In contrast, the C-terminal HEAT repeat domain is unable to recruit NIPBL to DSBs but independently targets NIPBL to laser microirradiation induced DNA damage...
February 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28166369/heterozygous-truncation-mutations-of-the-smc1a-gene-cause-a-severe-early-onset-epilepsy-with-cluster-seizures-in-females-detailed-phenotyping-of-10-new-cases
#10
Joseph D Symonds, Shelagh Joss, Kay A Metcalfe, Suresh Somarathi, Jamie Cruden, Anita M Devlin, Alan Donaldson, Nataliya DiDonato, David Fitzpatrick, Frank J Kaiser, Anne K Lampe, Melissa M Lees, Ailsa McLellan, Tara Montgomery, Vivek Mundada, Lesley Nairn, Ajoy Sarkar, Jens Schallner, Jelena Pozojevic, Ilaria Parenti, Jeen Tan, Peter Turnpenny, William P Whitehouse, Sameer M Zuberi
OBJECTIVE: The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS)...
February 6, 2017: Epilepsia
https://www.readbyqxmd.com/read/28159788/revisiting-the-regulation-of-the-primary-scaffoldin-gene-in-clostridium-thermocellum
#11
Lizett Ortiz de Ora, Iván Muñoz-Gutiérrez, Edward A Bayer, Yuval Shoham, Raphael Lamed, Ilya Borovok
: Cellulosomes are considered to be one of the most efficient systems for degradation of plant cell-wall polysaccharides. The central cellulosome component comprises a large, noncatalytic, protein subunit called scaffoldin. Multiple saccharolytic enzymes are incorporated into the scaffoldins via specific high-affinity cohesin-dockerin interactions. Recently, the regulation of genes encoding certain cellulosomal components by multiple RNA polymerase alternative σ(I) factors has been demonstrated in Clostridium (Ruminiclostridium) thermocellum In the present report, we provide experimental evidence demonstrating that the C...
February 3, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28154080/bacillus-subtilis-smc-complexes-juxtapose-chromosome-arms-as-they-travel-from-origin-to-terminus
#12
Xindan Wang, Hugo B Brandão, Tung B K Le, Michael T Laub, David Z Rudner
Structural maintenance of chromosomes (SMC) complexes play critical roles in chromosome dynamics in virtually all organisms, but how they function remains poorly understood. In the bacterium Bacillus subtilis, SMC-condensin complexes are topologically loaded at centromeric sites adjacent to the replication origin. Here we provide evidence that these ring-shaped assemblies tether the left and right chromosome arms together while traveling from the origin to the terminus (>2 megabases) at rates >50 kilobases per minute...
February 3, 2017: Science
https://www.readbyqxmd.com/read/28152414/coexisting-and-cooperating-mutations-in-npm1-mutated-acute-myeloid-leukemia
#13
Jay L Patel, Jonathan A Schumacher, Kimberly Frizzell, Shelly Sorrells, Wei Shen, Adam Clayton, Rakhi Jattani, Todd W Kelley
NPM1 insertion mutations represent a common recurrent genetic abnormality in acute myeloid leukemia (AML) patients. The frequency of these mutations varies from approximately 30% overall up to 50% in patients with a normal karyotype. Several recent studies have exploited advances in massively parallel sequencing technology to shed light on the complex genomic landscape of AML. We hypothesize that variant allele fraction (VAF) data derived from massively parallel sequencing studies may provide further insights into the clonal architecture and pathogenesis of NPM1-driven leukemogenesis...
January 23, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28137853/binding-sliding-and-function-of-cohesin-during-transcriptional-activation
#14
Melinda S Borrie, John S Campor, Hansa Joshi, Marc R Gartenberg
The ring-shaped cohesin complex orchestrates long-range DNA interactions to mediate sister chromatid cohesion and other aspects of chromosome structure and function. In the yeast Saccharomyces cerevisiae, the complex binds discrete sites along chromosomes, including positions within and around genes. Transcriptional activity redistributes the complex to the 3' ends of convergently oriented gene pairs. Despite the wealth of information about where cohesin binds, little is known about cohesion at individual chromosomal binding sites and how transcription affects cohesion when cohesin complexes redistribute...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137757/arabidopsis-homologue-of-scc4-mau2-is-essential-for-plant-embryogenesis
#15
Elena A Minina, Salim Hossain Reza, Emilio Gutierrez-Beltran, Pernilla H Elander, Peter V Bozhkov, Panagiotis N Moschou
Factors regulating dynamics of chromatin structure have direct impact on expression of genetic information. Cohesin is a multi-subunit protein complex crucial for pairing sister chromatids during cell division, DNA repair and regulation of gene transcription and silencing. In non-plant species cohesin is loaded on chromatin by the Scc2/Scc4 (NIBPL/MAU2) complex. Here we identify AtSCC4, the Arabidopsis homolog of Scc4, and show that it forms a functional complex with AtSCC2, the homolog of Scc2. We demonstrate that AtSCC2 and AtSCC4 act in the same pathway and that both proteins are indispensable for cell fate determination during early stages of embryo development...
January 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28134253/specialized-interfaces-of-smc5-6-control-hinge-stability-and-dna-association
#16
Aaron Alt, Hung Q Dang, Owen S Wells, Luis M Polo, Matt A Smith, Grant A McGregor, Thomas Welte, Alan R Lehmann, Laurence H Pearl, Johanne M Murray, Antony W Oliver
The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure-which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual 'molecular latch' and a functional 'hub'...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28120103/mutations-in-chromatin-regulators-functionally-link-cornelia-de-lange-syndrome-and-clinically-overlapping-phenotypes
#17
Ilaria Parenti, María E Teresa-Rodrigo, Jelena Pozojevic, Sara Ruiz Gil, Ingrid Bader, Diana Braunholz, Nuria C Bramswig, Cristina Gervasini, Lidia Larizza, Lutz Pfeiffer, Ferda Ozkinay, Feliciano Ramos, Benedikt Reiz, Olaf Rittinger, Tim M Strom, Erwan Watrin, Kerstin Wendt, Dagmar Wieczorek, Bernd Wollnik, Carolina Baquero-Montoya, Juan Pié, Matthew A Deardorff, Gabriele Gillessen-Kaesbach, Frank J Kaiser
The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex...
January 24, 2017: Human Genetics
https://www.readbyqxmd.com/read/28119487/stag1-mutations-cause-a-novel-cohesinopathy-characterised-by-unspecific-syndromic-intellectual-disability
#18
Daphné Lehalle, Anne-Laure Mosca-Boidron, Amber Begtrup, Odile Boute-Benejean, Perrine Charles, Megan T Cho, Amanda Clarkson, Orrin Devinsky, Yannis Duffourd, Laurence Duplomb-Jego, Bénédicte Gérard, Aurélia Jacquette, Paul Kuentz, Alice Masurel-Paulet, Carey McDougall, Sébastien Moutton, Hilde Olivié, Soo-Mi Park, Anita Rauch, Nicole Revencu, Jean-Baptiste Rivière, Karol Rubin, Ingrid Simonic, Deborah J Shears, Thomas Smol, Ana Lisa Taylor Tavares, Paulien Terhal, Julien Thevenon, Koen Van Gassen, Catherine Vincent-Delorme, Marjolein H Willemsen, Golder N Wilson, Elaine Zackai, Christiane Zweier, Patrick Callier, Christel Thauvin-Robinet, Laurence Faivre
BACKGROUND: Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations. METHODS: Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the local diagnostic standards...
January 24, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28118058/smc1%C3%AE-is-required-for-activation-of-sac-during-mouse-oocyte-meiosis
#19
Yilong Miao, Changyin Zhou, Zhaokang Cui, Xiaoxin Dai, Mianqun Zhang, Yajuan Lu, Bo Xiong
Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28116354/asxl1-interacts-with-the-cohesin-complex-to-maintain-chromatid-separation-and-gene-expression-for-normal-hematopoiesis
#20
Zhaomin Li, Peng Zhang, Aimin Yan, Zhengyu Guo, Yuguang Ban, Jin Li, Shi Chen, Hui Yang, Yongzheng He, Jianping Li, Ying Guo, Wen Zhang, Ehsan Hajiramezanali, Huangda An, Darlene Fajardo, J William Harbour, Yijun Ruan, Stephen D Nimer, Peng Yu, Xi Chen, Mingjiang Xu, Feng-Chun Yang
ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin(-)cKit(+) (LK) cells...
January 2017: Science Advances
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