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The Cell Nucleus
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The evolutional significance The formation of nucleus was an essential event in evolution. Containing nucleus or not is an important difference between eucaryotic cells and procaryotic cells. Nucleus prevent DNA from being damaged by enzymes in cytosol and make the performance of gene transcription and translation in different times and spaces.
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Topics Chromatin and chromosome Structure of nucleus The Transport of Molecules into and out of the Nucleus Nucleolus and the assemblage of ribosome
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What you should know when finish The form of genetic information in cell and what they are looking like before transcription and replication. The precise scheme of nuclear Features of nuclear pores Location signal Ribosome-producing machine and production of ribosome.
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Chromatin and chromosome Stainable material of interphase nucleus consisting of nucleic acid and associated basic protein called chromatin, which is dispersed through much of the nucleus. Further folding and compaction of chromatin during mitosis produces the visible metaphase chromosomes.
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epithelial cellHela cell Epithelial cell and Hela cell
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Kinds of chromatin Euchromatin and heterochromatin Euchromatin is loosely packed and accessible to RNA polymerases, whereas heterochromatin is highly condensed and probably transcriptionally inactive.
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Chemical components of chromatin DNA Each DNA molecule forms chromosome must contain three functional elements in order to replicate and segregate correctly: replication origins(several), the centromere(one), telomeres(two).
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replication origins at which DNA polymerases and other proteins initiate synthesis of DNA. centromere attachs any chromosome that contains it to mitotic spindle during M phase and guarantees the proper separation of chromosomes. telomeres permit a linear chromosome to be completely replicated.
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three functional elements
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Replication fork
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Histone The most abundant proteins associated with eukaryotic DNA. Five major types of histone proteins termed H1, H2A, H2B, H3, and H4 Rich in positively charged basic amino acids Conserved proteins except for H1 Nucleosomal histones and H1 histone
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Modification of histone influence chromatin structure participate in the regulation of transcription (1)acetylation and deacetylation Lys ε-NH 2 the greater the acetylation, the less chromatin condensation
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(2)methylation Lys ε-NH 2, Arg a process that pevents acetylation (3) phosphorylation Ser and Thr hydroxy introducing a negative charge
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Nonhiston Rich in acid amino acids Provide a structural scaffold for long chromatin loop Others: Transcription and replication factor HMG (high-mobility group) protein
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Packing of chromosome
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Primery Structure of Chromosome — nucleosome
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Structure protein core + DNA with diameter of 10nm The core is an octamer containing two copies each of histones H2A, H2B, H3, and H4. 147bp DNA protein core 60bp linker DNA beads-on-a-string form.
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The DNA component of nucleosomes is much less than is the linker DNA susceptible to nuclease digestion between them.
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nucleosome
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Histone tail
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Secondary Structure of Chromosome — Solenoid of nucleosomes approximately six nucleosomes per turn with a diameter of 30nm.
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Solenoid model
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The chromatin in chromosomal regions that are not being transcribed exists predominantly in the condensed, 30-nm fiber form. The regions of chromatin actively being transcribed are thought to assume the extended beads-on-a- string form.
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Tertiary Structure — Folded solenoid 30-nm chromatin fiber attach to chromatin scaffold
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Quaternary Structure — Chromatid
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Process of packing
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DNA ladder
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Structure of nucleus
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nuclear envelope outer membrane is continuous with ER and studded with ribosomes engaged in protein synthesis. inner membrane contains specific proteins that act as binding sites for the nuclear lamina inner and outer nuclear membranes are continuous, but maintain distinct protein compositions.
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perinuclear space
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nuclear lamina a meshwork composed by nuclear lamins A,B,C (a class of intermediate filaments) give shape and stability to the nuclear envelope provide anchor sites of chromatin phosphorylation of the nuclear lamins cause the nuclear lamina depolymerize
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nuclear pore complex pore complex contains one or more open aqueous channels (9nm in diameter and 15 nm long) through which water-soluble molecules that are smaller than a certain size can passively diffuse. Large molecules, such as DNA and RNA polymerases, ribosomal subunits, are actively transported.
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Diagram of NPC
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NPC
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Peering through the NPC
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nucleolus three partially segregated regions can be distinguished : (1) a pale-staining fibrillar center, which contains DNA that is not being actively transcribed;
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(2) a dense fibrillar component, which contains RNA molecules in the process of being synthesized (3) a granular component, which contains maturing ribosomal precursor particles.
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Nucleolus are formed by the fusion of RNA,rDNA and ribonucleoprotein coming from nucleolar organizing region. nucleolar organizing regions (NORs) are chromosomal fragments, located in certain chromosome(13,14,15,21,22), containing the gene of major RNA (18S,28S,5.8S).
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The size of the nucleolus reflects its transcriptional activity. Its size therefore varies greatly in different cells and can change in a single cell.
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nuclear matrix matrix might help organize chromosomes, localize genes, and regulate DNA transcription and replication within the nucleus.
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The transport of molecules into and out of the nucleus Through an aqueous channels whose diamenter is adjustable Bidirection: import and export Active and passive transportation Localization signal dependent
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NPC
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Nuclear Localization Signals,NLS
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SV40 T-antigen
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microinjection
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T-antigen
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Steroid hormone
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Nuclear import
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Nuclear Export Signals, NES
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mRNP
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The HIV Rev protein, which contains a NES, can override the restriction against transporting pre- mRNAs with unspliced splice sites
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Proteins imported to or exported from the nucleus contain NLS or NES. Proteins that shuttle between the nucleus and cytoplasm contain both signals.
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Pre-mRNAs bound by a spliceosome normally are not exported from the nucleus, assuring that only fully processed, functional mRNAs reach the cytoplasm for translation.
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Macromolecules Are Actively Transported into and out of the Nucleus Through Nuclear Pores
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It occurs through a large, regulated aqueous pore rather than through a protein transporter that spans one or more lipid bilayers. It is thought that a nuclear protein is transported through the pores while it is in a fully folded conformation.
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