BMS1025 Cell Biology - The Nucleus 2024 Lecture 1 PDF

BMS1025 – CELL BIOLOGY April Chloe Terrazas ; Cellular Biology: organelles, structure, function DR PENNY LYMPANY [email protected] 28AY04  CONTENT In these sess...

BMS1025 – CELL BIOLOGY April Chloe Terrazas ; Cellular Biology: organelles, structure, function DR PENNY LYMPANY [email protected] 28AY04  CONTENT In these sessions we will be looking at Nucleus – DNA packaging and chromatin Ribosomes and protein synthesis Endoplasmic reticulum This Photo by Unknown Author is licensed under CC BY WHY DO WE NEED TO KNOW? Cell biology Links to other areas of the Biochemistry course – Cell structure & BMS1025 organelles Biochemistry Pharmacology Structures of genes and other Pharmacology Molecular chromosomal structures will be biology covered in molecular biology in year 1 and 2 LEARNING OUTCOMES Identify features of the nucleus Describe the structures of the Endoplasmic Reticulum/Ribosomes Describe how DNA is packaged Describe how proteins are synthesised MORE INFORMATION AND READING LISTS For access to the Reading List for this module, go to the Course Materials page and click on reading list You can also use BibliU for your Reading List Source: Alberts et al. Molecular Biology of the Cell 7th Ed THE NUCLEUS Repository of genetic information and the cell’s control centre The nucleus is a membrane bound organelle in eukaryotic cells containing DNA Def: A eukaryote is an organism whose cells have a membrane- bound nucleus. All animals, plants, fungi, and many unicellular organisms are eukaryotes. DISCOVERY OF THE NUCLEUS Antony van Leeuwenhoek (1632– 1723) - probably the first to observe nucleus in the blood cells of birds and amphibians. Felice Fontana (1730–1805) - discoverer of nucleus by observing epidermal cells of eel Robert Brown, Scottish Botanist (1773–1858) observed the nucleus in plant cells and was the first to call these structures ‘nuclei’.  WHAT IS THE NUCLEUS? Key facts – contains DNA arranged in chromosomes surrounded by the nuclear envelope, a double nuclear membrane (outer and inner), which separates the nucleus from the cytoplasm nuclear membrane is supported by a meshwork of intermediate filaments (nuclear lamins) This Photo CC BY This Photo by Unknown Author is licensed under CC BY DNA def: Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. Nuclear envelope def: The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membranes: an inner nuclear membrane and an outer nuclear membrane. Nuclear Lamins def: fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear Source: Alberts et al. Molecular Biology of the Cell 7th Ed envelope.  WHAT IS THE NUCLEUS – CONT.? Key facts – outer membrane is continuous with the rough endoplasmic reticulum nuclear envelope contains pores which control the movement of substances in and out of the nucleus. RNA is selectively transported into the cytoplasm, This Photo CC BY This Photo by Unknown Author is licensed under CC BY proteins are selectively transported into the nucleus. RNA def: ribonucleic acid, a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins, although in some viruses RNA rather than DNA carries the genetic information. Source: Alberts et al. Molecular Biology of the Cell 7th Ed  WHY IS THE NUCLEUS IMPORTANT? Separates fragile chromosomes from cell contents – crucial for proper function of cell DNA replication, transcription and RNA processing - all in the nucleus Separates RNA transcription in the nucleus from translation machinery in the cytoplasm Nuclear envelope allows gene expression to be regulated mRNA undergoes posttranscriptional processing before moving from nucleus to cytoplasm control of gene expression at the level of transcription e.g. expression of some eukaryotic genes controlled by regulated transport of transcription factors from cytoplasm to nucleus  THE NUCLEUS – MORE INFORMATION Most cells have a single nucleus, some have none (i.e. red blood cells), and some have several (i.e. skeletal muscle) Nucleolus one or more nucleoli are found inside the nucleus most prominent in cells that are synthesising large amounts Nuclear lamins of protein sites at which ribosomes are assembled and ribosomal RNA is transcribed Nucleolus def: Largest structure in the nucleus of eukaryotic cells Site of ribosome biogenesis, which is the synthesis of ribosomes. Participates in the formation of signal recognition particles and plays a role in the cell's response to stress Ribosomes def: complex molecular machine that produce proteins from amino acids during protein synthesis or translation. Histology Guide © Faculty of Biological Sciences, University of Leeds THE NUCLEAR ENVELOPE Encloses DNA 2 concentric membranes- penetrated by nuclear pore complexes Inner membrane contains proteins that act as anchoring sites for chromatin and for the nuclear lamina outer membrane – continuous with ER and studded with ribosomes Perinuclear space Proteins made are transported into perinuclear space Chromatin def: a complex of DNA and protein found in eukaryotic cells. primary function is Source: Alberts 7th Edn Fig. 12-54 to package DNA molecules into more compact, denser structures.  NUCLEAR ENVELOPE DURING MITOSIS Nucleus disassembles, lamina depolymerises & NPCs disperse in cytosol Some NPC proteins bound to nuclear import receptors – important in reassembly of NPCs at end of mitosis Nuclear envelope membrane proteins disperse throughout ER membrane Later in mitosis, nuclear envelope reassembles close to surface of chromosomes TRANSPORT BETWEEN THE NUCLEUS AND THE CYTOSOL NUCLEUS CYTOSOL NUCLEAR PORES & NUCLEAR PORE COMPLEX Each nuclear pore complex (NPC) ~30 proteins (nucleoporins) Eightfold rotational symmetry A – 8-fold symmetry, proteins making up central portion of NPC orientated symmetrically – nuclear and cytosolic sides look identical. B – SEM of nuclear side of nuclear envelope C – EM of side view of 2 NPCs Source: Fig 12-55 Alberts et al. Molecular Biology of the Cell 7th Ed D – Face on view of NPC (A, adapted from A. Hoelz et al., Annu. Rev. Biochem. 80:613–643, 2011. B, © 1992 M.W. Goldberg and T.D. Allen. Originally published in J. Cell Biol. https://www.doi.org/10.1083/jcb.119.6.1429. With permission from Rockefeller University Press. C, courtesy of Werner Franke and Ulrich Scheer. D, courtesy of Ron Milligan.)  NUCLEAR PORES & NUCLEAR PORE COMPLEX SUMMARY 3-4000 NPCs in typical mammalian cell ~ 1000 macromolecules/s in both directions simultaneously internal diameter ∼40 nm - large enough to accommodate ribosomal subunits Pore filled with unstructured protein - numerous repeats of phenylalanine–glycine (FG) motifs - weak affinity - gel-like mesh inside the NPC Mesh - sieve - restricts diffusion of large macromolecules but smaller molecules pass through Small molecules (