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Nucleus & Genome Organisation (Genome - Organisms complete set of DNA,…
Nucleus & Genome Organisation
Genome - Organisms complete set of DNA, including all its genes.
Each genome contains all the information needed to build and maintain that organism
Central Dogma
Information coded in DNA directs the synthesis of proteins.
DNA -> amino acid sequence of proteins
DNA consist of double helical sugar phosphate structure
2 strands help together by hydrogen bonding between A&T or C&G bases
Sugar = deoxyribose - ribose missing an oxygen atom at 2' position
Each DNA strand consists of alternating deoxyribose molecules connected by phosphodiester bond from 5' position to 3' position
Adenine & Thymine = 2 hydrogen bonds
Cytosine and Guanine = 3 hydrogen bonds
Gene - Basic physical and functional unity of heredity
Gene controls the transmission and expression of one or more traits.
Sequence classes in the human genome
1% protein coding genes
4% RNA genes, regulatory sequences
6% Heterochromatin
45% Transposon Based repeats
44% Other sequences
20,000 protein coding genes
6,000 RNA genes
Total 26,000 genes
Genes in bacteria are similar in size and usually short ~1Kb
Eukaryotes huge variation - few KB to over 2000 Kb
Nuclear pores
Large complex structures in the nuclear envelope
Double membrane
Regulates movement of macromolecules
Proteins and nucleic acid in an out of the nucleus
Eukaryotes
Organisms whose cells contain nuclei and other organelles enclosed by membranes
Prokaryotes
Single cell organisms lacking a membrane bound nucleus
Nuclear pore complex (NPC)
Embedded in the double membrane of the nuclear envelope
30 different components (nucleoporines)
Nuclear pore complex has 3 rings - each made of eight identical subunits
Nucleoplasmic face - joined by terminal ring - forms nuclear basket
Cytoplasmic face - cytoplasmic ring of NPC supports 8 cytoplasmin filaments
Centre of NPC - central plug or transporter proteins and spoke which connects the two rings together.
Mitochondrial Genome 16.6 Kb - Only 37 genes
The nucleus
Houses DNA
Direct synthesis of ribosomes and proteins
Enclosed in an envelope - 2 parallel membrane separated by inter-membrane space
Compartmentalised
Most prominent organell
Transport to and from the nucleus is mediated by the nuclear pores
RNA and ribosomal subunits have to enter the cytoplasm
Proteins must enter the nucleus
Pores made from large number of proteins (multiprotein complex)
Transport requires both energy and transporter proteins
2000-4000 nuclear pores per nucleus
Gated Transport
Proteins on transported through nuclear pores with specific signal
Mobile transporter proteins recognise appropriate targeting sequence
The interacts with nuclear pore
Ech pore can transport up to 500 molecules per sec
Allows transport in both directions at the same time
Pore must expand/distort
Vanish when the nucleus disassembles during mitosis and reform when nuclei reform
Nuclear Import
Large macromolecules carry sorting signals - NLS - nuclear localisation signals
Nuclear import receptor protein (NIRP or importin) binds the large NLS tagged macromolecule and direct it through the pore
This way proteins synthesised in cytoplasm but required in the nucleus are transported through the NPC into the nucleus
Role of GTPase ran in nuclear transport
GTPase is an enzyme that can bind and hydrolyse guanosine triphosphate (GTP)
Hydrolysis is the chemical breakdown of a compound due to reaction with water
-GTP hydrolysis by RAN provides energy for transport (GTP->GDP+Pi)
Nucleoplasmic Ran is predominantly in the GTP bound state
Most cytosolic Ran has GDP bound
Nuclear compartments
Mostly chromatin
Nucleoli - where ribosomes are made - form at specific DNA regions called Nucleolar Organiser Regions
Haploid Cell DNA content = 3x10power9 bp
Distance between 2 bases along DNA molecule is 0.34nm
In nucleosome 147bp of DNA are wrapped around a complex of 8 core histones molecules
Variable-lenth stretch of free DNA (8-114bp) separates adjacent nucleosomes.
Stabilised by one molecules of the linker histone H1 - string of beads
Histones are small, highly basic proteins.
Carry a positive charge
This gives them affinity for negative charged DNA
Chromosomal DNA is coiled hierarchically
30nm fibre corresponds to a linear condensation of the DNA molecule of 50 fold of it stretched out length
Further compaction of 1000 fold in interphase and 10,000 fold in metaphase through complexing with non-histone proteins.
Packaging details are not clear
-- DNA complexing with proteins forms a macromolecule complex called chromatin.
-Chromosomes maintain their individuality during the entire cell cycle
Fundamental units of eukaryotic genome organisation.
Transmission and appropriate expression of genetic information
Major changes during the cell cycle
Highly condensed during metaphase - gene expression shut down
Interphase chromatin extended to allow gene expression
Interphase to metaphase
Condensin complex
SMC complex
Topoisomerase II
Histone phosphorylation
HP1
2 forms of chromatin
Euchromatin
less condensed
can be transcribed
weak binding of histone H1 and acetylation of four types of nucleosomal histones
Heterochromatin
more condensed
cannot be transcribed
Tight histone H1 binding
distint post-translational modifications on histones
including methylation of histone H3 at lysine 9
Constitutive heterochromatin
genetically inactive\largely repetitive DNA
Found at centromeres, telomeres, Y chromosomes in mammals
Facultative heterochromatin
Sometimes active - decondensed
Sometimes inactive - condensed
Randomly inactive X chromosomes on somatic cells of female mammals
Histone Modification
Amino ends of histone proteins are called histone tails
Accessible to enzymes that modify particular amino acid reidues such as addition of one or more acetyl (COCH3) methyl (CH3) or phosphate groups to the amino acid,
H£ and H4 modifications are important to gene activity
Molecular structure of centromere
-Specific region visible as a narrow constriction
-serves as a central component of kineochore
Complex of DNA and protein which spindle fibre attach to move chromosomes in meiosis and mitosis
Tandem repeats of a family of related 170bp DNA sequences called alphoid DNA
Plasmids - small DNA molecules (1-200bp)
can replicate independently
can be transmitted from one bacterium to another - horizontal gene transfer
up to 1000 copy number per cell
Prokaryotes
-Nutritional opportunists
acquire compounds from local environment or synthesise them by enzymatic pathways
-gene regulation mediated by proteins
-react to local environmental signals by lowering or raising the transcription of specific genes
Recognise environmental conditions in which they should activate or repress the transcription of relevant genes
switch on and off the transcription of each specific gene or group of genes