Nucleus, chromatin and nucleolus

Transcription

1 Nucleus, chromatin and nucleolus

2 The nucleus is the cell s centre

3 Nucleus: a cell's center Structure of the nucleus: Function of the nucleus: - Stores the chromosomes (genetic material) Note: 2 kinds of genetic material: deoxyribonucleic acid (DNA) ribonucleic acid (RNA) - production of ribosomes in nucleolus - protection of DNA from damaging molecules or molecules that interfere with its processing - DNA replication and synthesis of messenger RNA (mrna)

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5 Cell Nucleus, compartmentalized DNA activity Nuclear pores allow communication Nuclear lamina and cytoskeleton mechanically support the nucleus

6 PROKARYOTES DNA Packaging Naked DNA - i.e. no nuclear membrane DNA is circular - attached to membrane EUKARYOTES Much more complicated than prokaryotes Require much more genetic information (DNA) DNA must be folded and packaged to fit in the nucleus Particularly true when cell undergoes division Utilize specialist proteins to bind to DNA - form CHROMATINS

7 Chromosome Organization Nucleus is not just a sack of DNA Nuclear membrane is supported by two networks of protein filaments An outer network (microtubules) An inner network - Nuclear lamina During interphase (between divisions) chromosomes attach to nuclear membrane and lamina to provide organization Nucleus also contains a nucleolus Synthesizes rrna Use parts of chromosomes that condense in the same region Nucleolus DOES NOT have it s own membrane

8 Chromosome Organization Nucleus Structure

9 relevance The nucleus is central to the functioning of the cell and therefore knowledge of it s structure is obviously important. Also this is the site of action of some medical drugs and therefore to understand how these drugs work you must understand first how the nucleus works.

10 overview The nucleus is the centre of cellular activity, containing chromosomal deoxyribonucleic acid [ DNA] and the systems for ribonucleic acid [ RNA] synthesis and processing that allow the information in the DNA to be expressed as specific proteins in the cytoplasm.

11 The nuclear envelope forms a barrier between the nucleus and the cytoplasm and contains pores for the passage of macromolecules.

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13 The nucleolus is a morphologically distinct region of the nucleus, specialised for the production of rrna.

14 The nucleus contains a large number of particles, most of which are complexes of RNA and protein, involved in the synthesis, processing, and transport of RNA transcribed from DNA.

15 The nucleus contains a matrix that provides a structural framework to facilitate and organize the complex events involved in RNA and DNA synthesis and processing.

16 Components of the nucleus

17 1, nuclear envelope The nuclear envelope forms a barrier between the nucleus and the cytoplasm and contains pores for the passage of macromolecules. Thus the nucleoplasm is seperated from the cytoplasm by a double membrane = the nuclear envelope.

18 The 2 membranes comprising the nuclear envelope both measure approximately 10 nm in thickness, and they are seperated by a gap of nm which is known as the perinuclear space. The outer nuclear membrane is continous with the endoplasmic reticulum and is often studded with ribosomes involved in protein synthesis.

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20 functionally similar to

21 1) The nuclear envelope consists of two nuclear membrane, an underlying nuclear lamina, and nuclear pore complexes. 2) The outer membrane is functionally similar to the membranes of the ER and has ribosomes bound to its cytoplasmic surface.

22 nuclear lamina an attachment site for

23 b)the inner nuclear membrane is lined by the nuclear lamina, which serves as an attachment site for chromatin.

24 At periodic intervals the inner and outer nuclear membranes appear to be fused together, forming nuclear pores, the average size of which is 100 nm although the size and spacing vary between nuclei. Each pore is composed of a nuclear pore complex measuring approximately 80 nm on the inside diameter, With an estimated open 9 nm channel

25 A typical mammalian cell contains 3000 to 4000 pore complexes in it s nuclear envelope. The pores generally occupy 1/3 of the surface of the nuclear envelope and allow for the passage of molecules into and out of the nucleus

26 Figure 8.2 Electron Micrograph Showing Nuclear Pores

27 Figure 8.3 Electron Micrograph of the Nuclear Lamina a meshwork of filaments underlying the inner nuclear membrane

28 Model of the Nuclear Pore Complex from 9 nm to as large as 40 nm

29 Changes in the conformation of the central channel during the passage of macromolecules change its opening from 9 nm to as large as 40 nm, which is wide enough to accommodate the largest particles able to cross the nuclear envelope.

30 Figure 8.6 Electron Micrograph of Nuclear Pore Complexes eightfold symmetry organized around a large central channel.

31 2, chromatin The genome is formed by 2 complementary strands of DNA arranged as a double helix and serves as a template for the synthesis of RNA molecules whose function is expressed in the cytoplasm. The DNA is complexed with proteins to form chromatin, only part of which, in any particular cell, is active in RNA synthesis. At cell division, the chromatin condenses further to form discrete chromosomes.

32 The Nuclear DNA of a cell is organized into discrete units termed chromosomes. Each chromosome is a single DNA molecule The DNA is not bare. It is coated and organized by a wide variety of proteins. Collectively, the DNA and protein assemblage that constitutes the chromosomes is referred to as chromatin

33 The nuclear proteins associated with DNA may be divided into 2 classes. 1,The histones 2, the non histone chromosome proteins The latter comprise a large and diverse assemblage of regulatory and structural proteins with a variety of functions.

34 Nucleosome: Subunit of chromatin composed of a short length of DNA wrapped around a core of histone proteins. The human genome contains about 3 billion nucleotide pairs organized as 23 chromosomes pairs. If uncoiled, the DNA contained by each of those chromosomes would measure between 1.7 and 8.5 cm (0.67 to 3.35 inches) long. This is too long to fit into a cell.

35 Moreover, if chromosomes were composed of extended DNA, it is difficult to imagine how the DNA could be replicated and segregated into two daughter cells without breaking down. In fact chromosomal DNA is packaged into a compact structure with the help of specialized proteins called histones. The complex DNA plus histones in eukaryotic cells is called chromatin.

36 The fundamental packing unit is known as a nucleosome. Each nucleosome is about 11nm in diameter. The DNA double helix wraps around a central core of eight histone protein molecules (an octamer) to form a single nucleosome. A second histone (H1 in the illustration) fastens the DNA to the nucleosome core.

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38 One of the primary purposes of the nucleosomes appears to be compacting DNA by supercoiling it into 30 nm filaments that in turn can be arranged into thicker fibres composed of spirals or solenoid arrangements.

39 Chromatin is the state of DNA in which it is tightly coiled up with histones, which keep it from being transcribed into mrnas. The nucleosome cores are seperated from each other by a region of linker DNA.

40 The Nucleosome Wound DNA Nucleosome Linker DNA Histone Core

41 A = 30nm fiber of an interphase chromosome B = Nucleosomes along a strand of DNA

42 The Histone tails are a critical determinant of chromatin structure

43 Solenoids Formation of chromatin allows the DNA to be packed into a solenoid Long solenoids then form LOOPS which are condensed (ROSETTES) that make up a CHROMOSOME

44 Chromosome Packaging 1. Nucleosomes 2. Solenoids 3. Loops 4. Rosettes 5. Chromosomes

45 Levels of Chromosome Structure

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48 Figure 8.18 Looped Chromatin Domains

49 Description of above picture Light micrograph of a chormosome of amphibian oocytes, showing decondensed loops of actively transcribed chromatin extending from an axis of highly condensed nontranscribed chromatin.

50 Clearance of nucleosomes from specific areas by chromatin remodelling complexes allows proteins access to the DNA

51 The 30nm fiber is organized to loops that can be opened up individually This allows individual genes and sets of genes to be accessed without a global unpacking of the chromosome

52 Heterochromain proteins condense the 30nm fiber into a more tightly packed structure

53 An individual gene is defined as the segment of DNA coding for an individual RNA or protein And the entire complement of DNA is called the genome.

54 Heterochromatin is commonly located in an irregular band around the nuclear periphery and around the nucleolus as well as in patches throughout the nucleoplasm

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56 In an average eukaryotic cell 90 % of the chromatin is transcriptionally inactive The 10% that is active is always in the form of euchromatin and this is responsible for providing the blue print for cellular products in the form of RNA molecules that leave the nucleus.

57 So The amount of heterochromatin present in the nucleus varies with transcriptional activity Little heterochromatin is present in transcriptionally active cancer cells. Whereas the nuclei of mature spermatazoa which are transcriptionally inactive are filled with condensed chromatin.

58 cell size and shape are more variable in cancer cells than in normal cells. Indentation, budding, elongation and furrowing are some of the features of the nucleus in tumour cells

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61 Central Dogma of Molecular Biology DNA RNA Protein

62 The mrna leaves the nucleus and travels to the cytoplasm, where it encounters cellular bodies called ribosomes. The mrna, which carries the gene's instructions, dictates the production of proteins by the ribosomes.

63 Protein Synthesis

64 3, the nucleolus The nucleolus is a morphologically distinct region of the nucleus, specialised for the production of rrna It is a distinct biochemical and structural entity in which specific genes and their products are sequestered from the rest of the genome. The primary function is the production and assembly of preribosomal subunits hence the high content of RNA and ribonucleoprotein.

65 Nucleolar shape, size and number vary depending on the organism, cell type and state of the cell. There is nucleolar hypertrophy in cancer cells [ but also any other hyperactive cells ] The nucleolus breaks down or decondenses during mitosis [ as r RNA synthesis stops]

66 The nucleolus consists of 4 areas A fibrillar region around Fibrillar centres A granular region A nucleolar matrix

67 Figure 8.24 Structure of the Nucleolus the fibrillar centers the dense fibrillar compnents granular component

68 1) Morphologically, nucleoli consist of three distinguishable regions: the fibrillar center, dense fibrillar component, and granular component. These different regions are thought to represent the sites of progressive stages of rrna transcription, processing, and ribosome assembly.

69 Thus in summary the nucleolus contains the nucleolar organiser which directs the synthesis of rrna needed for translation.

70 Nucleolus generally only detected in interphase as breaksdown for mitosis as r RNA synth stops then.

71 The Working Cell DNA, RNA and Protein Synthesis

72 The Central Dogma of Molecular Biology