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ORGANISATION OF EUKARYOTIC GENOME (STRUCTURE OF (DNA (of chromosome…
ORGANISATION OF EUKARYOTIC GENOME
STRUCTURE OF
size
larger size
10Mb to 100 000Mb
DNA
linear, double stranded
of chromosome
single, double stranded molecule (chromatid)
multiple origins of replication
increase rate of replication
because of large size
multiple chromosomes bound by nuclear membrane in nucleus
genes in chromosome
coding sequence (exons)
codes for functional proteins
each gene has it's own promoter
regulation of each gene occurs individually
exons interrupted by non-coding introns
function: allow for alternative splicing
allows one gene to code for multiple polypeptide
structure: 'GT-------AG'
in mitochondrial genome
circular, double stranded
CHROMOSOME
consists of
two identical sister chromatids
chromatids joined at CENTROMERES
constricted region of chromosome (220 nucleotides)
composed of highly repeated sequence
function
sister chromatid adhesion
kinetochore formation
kinetochore: complex of proteins forms at each centromere
attachment point for spindle fibres (separate sister chromatid during anaphase)
importance
aberrant function --> improper chromosomal alignment and segregation
aneuploidy (chromosomal aberration) (ref. protein synthesis mutation)
TELOMERES at the ends of chromosomes (end of DNA molecule)
Specialised DNA sequences
found at the end of linear DNA
already exists - NOT LIKE 5' CAPPING WHERE IT'S ADDED BUT IT IS ALREADY THERE
repeat of DNA sequence (5' TTAGGG3')
function
postpone erosion of genes via successive rounds of replication
caused by end replication problem (ref. protein synthesis)
telomeres shortened instead of critical genes
telomeres extended by telomerase
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act as buffers
prevent loss of crucial genes as chromosome shortens
prevent degradation of ends of linear DNA molecules by deoxyribonuclease
maintain integrity of chromosomal end
prevent fusion of chromosomal end between chromosomes
importance
fusion of exposed ends disrupts regulation of genes on adjoined chromosomes :
prevents DNA repair machinery from recognising and sticking together ends of chromosomes when there are chromosome breaks
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limit lifespan of cells
when critical length of telomere reached
cells undergo apoptosis
because in somatic cells telomerase is inactive
importance
limits extent of accumulated mutations
prevents development of cancerous cells
CONTROL ELEMENTS
PROMOTER
nucleotide sequence upstream of a gene
general transcription factors and RNA polymerase attach to initiate transcription of mRNA
ENHANCER
nucleotide sequence located far away (>1000bp) from transcription start site (upstream or downstream)
activator proteins attach to activate transcription
SILENCER
nucleotide sequence located far away (>1000bp) upstream of transcription start site
repressor proteins attach to suppress transcription
ORGANISATION
Formation of Nucleosome
Formation of solenoid fibre (30m chromatin)
linker DNA joins adjacent nucleosomes (brings nucleosomes together)
DNA not associated with histones (in between nucleosome) is linker DNA
coiling
of nucleosomes into a helical structure
chromatin packed together into one long rope like structure (FYI)
Formation of loop domains
solenoid structure forms loops anchored by non-histone scaffolding proteins
formation of chromosome
scaffolding proteins further coiled and folded
negatively charged DNA winds around the outside of positively charged histone proteins
H1 histone fastens DNA to nucleosome core
nucleosome core: histone cramer (8 histones that DNA is wrapped around)
nucleosome: fundamental unit of chromatin
structure: beads on a string
occurs during prophase
of chromtatin
EUCHROMATIN
lightly condensed
nucleosome structure (level of coiling)
parts lack nucleosome (just DNA) so other proteins and transcription factors can bind to DNA
allows access of RNA polymerase to transcribe the genes
genes are
actively expressed
appear in light microscope:
lightly stained
region
HETEROCHROMATIN
highly condensed form
solenoid and more condensed structures
genes not expressed
structure of DNA
structure: transcriptionally inactive genes
doesn't allow access to RNA polymerase and transcription factors (because compact)
structure: made up of repetitive sequences and don't contain genes
concentrated in centromeres and telomeres
CONTROLLED BY
chemical modification of DNA and histone proteins
histone: changes charge and affects association between DNA (ref. nucleosome formation)