Cohesin
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Cohesin
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB. Cohesin was separately discovered in budding yeast by Douglas Koshland and Kim Nasmyth. Structure Cohesin is a multi-subunit protein complex, made up of SMC1, SMC3, RAD21 and SCC3 (SA1 or SA2). SMC1 and SMC3 are members of the Structural Maintenance of Chromosomes (SMC) family. SMC proteins have two main structural characteristics: an ATP-binding cassette-like 'head' domain with ATPase activity (form ...
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RAD21
Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the ''RAD21'' gene. ''RAD21'' (also known as ''Mcd1'', ''Scc1'', ''KIAA0078'', ''NXP1'', ''HR21''), an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans.  RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 STAG1 (SA1) and STAG2">STAG1.html" ;"title="STAG1">STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in Establishment of sister chromatid cohesion, sister chromatid cohesion. Discovery ''rad21'' was first cloned by Birkenbihl and Subramani in 1992 by complementing the radiation sensitivity of the ''rad21-45'' mutant fission yeast, '' Schizosaccharomyces pombe'', and the murine and human homologs of ''S. pombe'' rad21 were cloned by McKay, Troelstra, van der Spek, Kanaar, Smit, Hagemeijer ...
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Cohesin
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB. Cohesin was separately discovered in budding yeast by Douglas Koshland and Kim Nasmyth. Structure Cohesin is a multi-subunit protein complex, made up of SMC1, SMC3, RAD21 and SCC3 (SA1 or SA2). SMC1 and SMC3 are members of the Structural Maintenance of Chromosomes (SMC) family. SMC proteins have two main structural characteristics: an ATP-binding cassette-like 'head' domain with ATPase activity (form ...
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Establishment Of Sister Chromatid Cohesion
Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles. Cohesin loading Cohesin first associates with the chromosomes during G1 phase. The cohesin ring is composed of two SMC (structural maintenance of chromosomes) proteins and two additional Scc proteins. Cohesin may originally interact with chromosomes via the ATPase domains of the SMC proteins. In yeast, the loading of cohesin on the chromosomes depends on proteins Scc2 and Scc4. Cohesi ...
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Topologically Associating Domain
A topologically associating domain (TAD) is a self-interacting genomic region, meaning that DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. The median size of a TAD in mouse cells is 880 kb, and they have similar sizes in non-mammalian species. Boundaries at both side of these domains are conserved between different mammalian cell types and even across species and are highly enriched with CCCTC-binding factor (CTCF) and cohesin. In addition, some types of genes (such as transfer RNA genes and housekeeping genes) appear near TAD boundaries more often than would be expected by chance. The functions of TADs are not fully understood and are still a matter of debate. Most of the studies indicate TADs regulate gene expression by limiting the enhancer- promoter interaction to each TAD, however, a recent study uncouples TAD organization and gene expression. Disruption of TAD boundaries are found to be associated with ...
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SMC1A
Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the ''SMC1A'' gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3. SMC1A is a member of the SMC protein family. Members of this family are key regulators of DNA repair, chromosome condensation and chromosome segregation from bacteria to humans. Structure The domain organisation of SMC proteins is highly conserved and is composed of an N-terminal Walker A motif, coiled-coil, "hinge", coiled-coil and a C-terminal Walker B motif. The protein folds back on itself to form a rod-shaped molecule with a heterodimerisation "hinge" domain at one end and an ABC-type ATPase "head" at the other. These globular domains are separated by a ~50 nm anti-parallel ...
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NIPBL
Nipped-B-like protein (NIPBL), also known as SCC2 or delangin is a protein that in humans is encoded by the ''NIPBL'' gene. NIPBL is required for the association of cohesin with DNA and is the major subunit of the cohesin loading complex. Heterozygous mutations in ''NIPBL'' account for an estimated 60% of case of Cornelia de Lange Syndrome. Structure and Interactions NIPBL is a large hook-shaped protein containing HEAT repeats. NIPBL forms a complex with MAU2 (Scc4 in budding yeast) known as the cohesin loading complex. As this name suggests NIPBL and MAU2 are required for the initial association of cohesin with DNA. Cohesin is thought to mediate enhancer-promoter interactions and generate Topologically associating domains (TADs). As well as mediating cohesion and regulating DNA architecture the cohesin complex is required for DNA repair by homologous recombination. Given that NIPBL is required for cohesin's association with DNA it is thought that NIPBL is also required for a ...
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Kim Nasmyth
Kim Ashley Nasmyth (born 18 October 1952) is an English geneticist, the Whitley Professor of Biochemistry at the University of Oxford, a Fellow of Trinity College, Oxford, former scientific director of the Research Institute of Molecular Pathology (IMP), and former head of the Department of Biochemistry, University of Oxford. He is best known for his work on the segregation of chromosomes during cell division. Early life and education Nasmyth was born in London in 1952 of James Ashley (Jan) Nasmyth and Jenny Hughes. His father Jan was doubly descended from King Charles II and founder of the billion dollar publishing company Argus Media. He attended Eton College, Berkshire, then the University of York, where he studied Biology. Nasmyth went on to complete his graduate studies in the group of Murdoch Mitchison at the University of Edinburgh. Here he worked on the cell cycle alongside Paul Nurse and his PhD thesis focused on the control of DNA replication in fission yeast. In ...
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SMC Proteins
SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions: * A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion. * Likewise, a pair of SMC2 and SMC4 acts as the core of the condensin complexes implicated in chromosome condensation. * A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses. Each complex contains a distinct set of non-SMC regulatory subunits. Some organisms have variants of SMC proteins. For instance, mammals have a meiosis-specific variant of SMC1, known as SMC1β. The nematode ''Caenorhabditis elegans'' has an SMC4-variant t ...
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SMC Protein
SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions: * A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion. * Likewise, a pair of SMC2 and SMC4 acts as the core of the condensin complexes implicated in chromosome condensation. * A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses. Each complex contains a distinct set of non-SMC regulatory subunits. Some organisms have variants of SMC proteins. For instance, mammals have a meiosis-specific variant of SMC1, known as SMC1β. The nematode ''Caenorhabditis elegans'' has an SMC4-variant t ...
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Meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome ( haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote. Errors in meiosis resulting in aneuploidy (an abnormal number of chromosomes) are the leading known cause of miscarriage and the most frequent genetic cause of developmental disabilities. In meiosis, DNA replication is followed by two rounds of cell division to produce four daughter cells, each with half the number ...
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Meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome ( haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote. Errors in meiosis resulting in aneuploidy (an abnormal number of chromosomes) are the leading known cause of miscarriage and the most frequent genetic cause of developmental disabilities. In meiosis, DNA replication is followed by two rounds of cell division to produce four daughter cells, each with half the number ...
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STAG2
Cohesin subunit SA-2 (SA2) is a protein that in humans is encoded by the ''STAG2'' gene. SA2 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3. ''STAG2'' is frequently mutated in a range of cancers and several other disorders. Function SA2 is part of the cohesin complex, which is a structure that holds the sister chromatids together after DNA replication. STAG2 has been shown to interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ... with STAG1. Role in Disease Of the cohesin complex, STAG2 is the subunit where the most variants have been reported ...
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