L04 nucleus

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L04 nucleus

  1. 1. Structure of cell nucleus, nuclear receptors and intracellular signalling
  2. 2. Nucleus : stru c tur e a nd func tion <ul><li>Nucleus in a human cell </li></ul><ul><li>- diameter 5-8  m </li></ul><ul><li>- 10% of a total cell volume </li></ul><ul><li>- DNA size - 3x10 9 pb, length </li></ul><ul><li>2 m, 23 chromosome pairs </li></ul><ul><li>- </li></ul><ul><li>Important metabolic processes DNA replication transcription RNA processing formation of ribosomal subunits </li></ul>Ultrathin section Freeze fracture ne nucleolus np
  3. 3. Nuclear DNA is packaged into chromosomes <ul><li>Eu c aryotic chromosome </li></ul><ul><li>a single, long, linear DNA molecule associated with proteins to a more compact structure. Some of the proteins are involved in DNA packaging, other take part in gene expressing, replication and repair. </li></ul><ul><li> P ro c aryotic chromosome: circular DNA lacking proteins </li></ul>Mitotic chromosomes as seen in a scanning electron microscope
  4. 4. Chromosome: a complex of DNA and proteins (chromatin). Basic units are nucleosomes Nucleosomes  protein core made of 8 histone molecules: 2 copies of H2A,H2B, H3 a H4  DNA Histones: Small proteins with a high proportion of positively charged amino acids – lysine and arginine. These positive charges help the histone bind tightly to the negatively charged sugar-phosphate backbone of DNA
  5. 5. Levels of chromatin packing 1. naked DNA molecule - does not occur in vivo 2. beads-on-a-string occurs teporarily during transcription 3. nucleosomes condensed into 30 nm thread due to a binding od H1 histone 4. Organization of the 300 nm thread from loops along a central axis. Non-histon proteins are involved 5. Formation od secondary loops to form a 700 nm thread 6. Metaphasic chromosome 1400 nm thick ( role of condensin)
  6. 6. Lidské chromosomy Mitotic chromosomes from human lymphocytes Chromosomes: homologous nonhomologous Chromosome identification: banding FISH: fluorescence in situ hybridization
  7. 7. The three DNA sequence elements needed to produce a eucaryotic chromosome that can be replicated and then segregated at mitosis
  8. 8. Interphase nucleus: nuclear envelope nuclear lamina nuclear matrix nuclear pores IF ER MT Heterochromatin highly condensed, transriptionally inactive Euchromatin decondensed in interphase condensed during mitosis
  9. 9. The nuclear pore complex The nuclear envelope is perforated b y n. pores – the gates for entering or leaving molecules of RNA or proteins NP is composed of about 100 different proteins and forms a short channel with protruding protein fibrils Small molecules – nucleoti-des, ATP and others enter freely. Large molecules require an appropriate sorting signal (nuclear localization signal)
  10. 10. Topolog y of biochemical pro c esses in the nucleus Chromosom al domains - each chromosome occupies a defined sector of the nuclear space „Movement“ of chromosom es is experimentall y proved – tagged centromeres or telomeres change their position to the NE Transcription: RNA polymerase I – nucleolus RNA polymerase II and I II – nucleoplasm (small compartments 40-100 nm in diameter) A ssembly of ribosomal subunits: nucleolus DNA replication: replication foci along the chromosomes 1 replication focus contains some 5 replicons, velocity of the replication - 2kbp/min during S phase some 10 000 replication foci are operating in the nucleus
  11. 11. Topology of interphase chromosomes in the nucleus Each chromosome occupies a particular region of the nucleus so that the chromosomes are not entangled with each other. The chromosomes are attached to a NE or nuclear lamina via proteins of the inner membrane NE: lamin B receptor (LBR) or lamina – associated protein (LAP2). To these proteins c hromatin and lamins are bound
  12. 12. Nucleolus a region where the parts of different chromosomes carrying genes for ribosomal RNA cluster together. Here the genes are transcribed and ribosomal subunits are assembled (using ribosomal proteins imported from the cytoplasm
  13. 13. Nuclear receptors <ul><li>Common term for intracellular (mostly intranuclear ) receptors, binding hormones soluble in lipids– e.g. steroids, thyroid hormones , vitamine D or retinoids </li></ul><ul><li>Nuclear receptors are proteins that after binding of ligand (steroid molecules) undergo structural changes and may function as transcription factors </li></ul>
  14. 14. Nucleus and signal transduction pathway
  15. 15. Nuclear receptors as transcription factors
  16. 16. Nucleus and signal transduction pathway
  17. 17. Nuclear receptors <ul><li>Common term for intracellular receptors binding hormones soluble in lipids– e.g. steroids, thyroid hormones ; vitamine D or retinoids </li></ul><ul><li>Nuclear receptors are proteins that after binding of ligand (e.g. steroid molecules) undergo structural changes and may function as transcription factors, binding to specific DNA sequences. </li></ul>
  18. 18. Nuclear receptors as transcription factors
  19. 19. Key terms 1. Overall structure and function of the human cell nucleus 2. Chromosome structure as seen in the optical microscope. 3. Cytochemical identification of single chromosomes 4. Three sequence elements of chromosomal DNA 5. Molecular arrangement of DNA and histones in the chromosome 6. Levels of chromosome condensation 7. Ultrastructure of the nuclear surface and nuclear pores 8. Nucleolus. 9. Topology of chromosomes in the nucleoplasm 10. Nucleus and intracelular signalling 11. Nuclear receptors as transcription factors
  20. 21. Vyštěpující tělísko Heterochromatin PcG tělísko Cajalovo (svinuté) tělísko a Gem Chromosomální teritoria PML tělísko Jaderné skvrny SAM68 tělísko Perinukleární kompartment Jadérka Periferní jaderná lamina RNA pol II transkripční faktor OPT doména Komplex jaderného póru JADERNÉ DOMÉNY

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