DNA and genes Flashcards
3 components of a nucleotide
- phosphate
- sugar
- nitrogenous base
2 types of base
- pyramidine
- purine
purine bases
A G
pyramidine bases
C, T, U
how many double bonds between G and C
3
how many double bonds between A and T
2
Protein in chromatin which compacts DNA
Histone
components of the histone core
2 x H2a
2x H2b
2 x H3
2 x H4
Name of top arm of chromatid
p
name of bottom arm of chromatid
q
in which phase of the cell cycle does DNA replication occur?
S phase
DNA replication - which enzyme breaks H bonds between bases
DNA helicase
DNA replication - where do proteins bind to stop the strands from joining back up?
replication fork
In the leading strand which direction does DNA replication occur?
5’ to 3’
DNA replication - what binds to the 3’ parent strand?
RNA primer
what produces the RNA primer?
DNA primase
DNA replication - which enzyme attaches to the RNA primer to add base pairs on the leading strand?
DNA polymerase alpha
DNA replication - What degrades RNA primer ?
RNAse H
DNA replication - which enzyme joins the strands together at the end?
DNA ligase
what is epigenetics?
heritable changes which are expressed - but not caused by a change in the DNA sequence
2 applications of DNA replication
1) PCR
2) Sanger method
Which RNA polymerase produces rRNA?
RNA P 1
what does RNA P 2 form?
mRNA
what does RNA 3 form?
tRNA + small ribosome RNA molecules
3 stages where gene expression is regulated?
- transcription
- splicing
- translation
Transcription - what binds with promoters in DNA
RNA polymerase
Transcription - which enzyme breaks H bonds between strands?
RNA polymerase
Transcription - what RNA is formed?
mRNA
how does mRNA leave the nucleus?
nuclear pores
what 2 things occur during mRNA processing?
1) capped 5’
2) cleaved 3’
what occurs during capping?
- P
+ methylated guanine molecule
what occurs during cleaving?
+ 200 nucleotide tail via poly-A-polymerase
which 2 things attach to the intron during splicing?
splicesosome + SnRNPs
how do transcription factors affect gene expression?
increase it
where do transcription factors bind to on the gene?
promoter region
2 mechanisms of transcriptional control
1) switching on a gene
2) switching off a gene
2 ways genes can be switched off
1) repressor binds next to transcription activator
2) repressor binds in the transcription activators place - inhibition
in which organ is the WTP transcription factor present?
Kidney
which gene does the WTP join to?
EGR-1 gene
effect of WTP and EGR-1 joining?
switches of EGR-1 expression
when WTP is mutated what can it cause and why?
kidney tumours - due to uncontrolled EGR-1 expression
what are the stop codons?
AGA, UAA, UAG
what is the start codon?
AUG - met
how is translation controlled?
mRNA degradation
how are isoforms formed?
alternative gene splicing
what proteins do tertiary structures form? (2)
- fibrous
2. globular
what are proproteins?
proteins which are inactive until activated by post-translational modifications (PTM)
example of proprotein activation
insulin
what enzyme removes signal recognition peptide?
signal peptidase
SCALP
s - addition of small groups c - proteolytic cleavage a - AA change chemical structure l - addition of long groups p - proline isomerisation
in proteolytic cleavage, at which bond is it cleaved?
peptide
where can the proteolytic cleavage occur?
N - terminus or internally
what is proline isomerisation?
Cis and trans transformation of proline
where is phosphate donated from in phosphorylation?
ATP
what enzyme adds phosphates?
protein kinase
what enzyme removes phosphate?
protein phosphotase
when is phosphorylatation used? - biological process
- activating pyruvate
- EGF
- CDKs
what enzyme adds acetyl groups?
protein acetyltransferase
what enzyme removes acetyl groups?
protein deACetylase
when is acetylation used?
- histones
- gene transcription
where is methyl groups taken from?
s-adenosyl-methionine
which enzyme adds methyl groups?
methyltransferase
which enzyme removes methyl groups?
protein demethylase
2 processes of addition of large functional groups
1) glycosylation
2) mono-poly ubiquitination
what is added to a protein to create a glycoprotein?
sugar - poly/monosaccaride
what protein is added in ubiquitination?
ubiquitin
what amino acid of the ubiquitin is added to the lysine of a protein?
Glycine
if one ubiquitin protein is added, what occurs?
change in protein structure
if many ubiquitin proteins are added, what occurs?
protein degradation
what does the E1 ubiquitin enzyme do?
allows joining of ubiquitin and substrate
which enzyme catalyses the functioning of ubiquitin?
E2 - conjugating enzyme
which enzyme is involved in deubiquitination of proteins?
proteosome
2 uses of polyubiquitinisation
- removal/degradtion of faulty proteins
2. controls protein lifespan
what is lipidation?
adding lipids or fatty acids
why are lipids added to proteins?
to make them soluble to pass through the plasma membrane
4 diseases caused by errors in gene expression
- cystic fibrosis
- spinal muscular atropy
- duchene muscular dystrophy
- pulmonary arterial hypertension
mutated gene in cystic fibrosis?
CFTR
mutated gene in spinal muscular atrophy?
SMN1
mutated gene in duchene muscular dystrophy
DMD
mutated gene in pulmonary arterial hypertension?
BMPR2
what can be caused if there is over-expression of transcription factors?
cancer
what is haplionsuffiency?
when 1 copy of the gene is not sufficient for protection
disease caused by mRNA processing error?
Cystic fibrosis
in what specific process does cystic fibrosis gene arror occur?
alternative splicing
which exon is skipped in the CFTR gene to cause CF?
7
2 techniques to detect DNA, RNA and proteins
1) gel electrophoresis
2) western/southern blot
what is DNA polymorphism?
DNA variation
5 ways mutations arise:
- strand breakage
- base loss
- base change
- DNA cross-linking
- DNA replication error
which bond is broken in base loss?
glycosidic bond
in base changes, what is C changed to?
U
which agents cause DNA cross-linking?
- UV light
- Anti-cancer agents
3 types of mutation;
- point
- indel
- chromosomal
which type of mutation affects a couple of nucleotides
indel mutation
3 types of chromosomal mutations
- polyploidy
- aneuploidy
- chromosome rearrangements
which chromosomal mutation involves a few chromosomes
polyploidy
what is aneuploidy chromosomal mutations?
abnormal number of extra/missing chromosomes
difference between missense and nonsense mutations
missense = results in loss/gain of function nonsense = results in non-functional protein
what type of codon arises in nonsense mutations
STOP
which point mutation results in pulmonary hypertension?
missense - loss of funtion
which point mutation results in achondrioplasia?
missense - gain of function
what disease is caused by a non-sense mutation?
Duchene muscular dystrophy
what is used to identify mutations?
electropherogram
what is a simple tandon repeat?
same part of a sequence repeated many times
example of simple tandon repeat disease
Huntingtons
in what gene are the repeats in huntingtons disease?
IT15 gene
what is a transposon?
a sequence of DNA which can move around the gene
transposon which copies and pastes
retroposon
What does a DNA transposon do?
cut and paste DNA sequences
example of Alu repeats
Cholesterol (LDL)
what is a selective pressure?
diseases which have a protective effect
which disorder protects against sickle cell anaemia?
Malaria
what is the open reading frame?
region between start and stop codon
2 types of protein secretion
1) constitutive (non-regulatory)
2) regulated
what is translocation?
movement of protein to the site of action
what are the 2 translocation pathways?
1) direct
2) secretory
what is the direct translocation pathways?
cytosol, mitochondria, nucleus, perioxsomes
where does post translational modifications occur?
Golgi
where do the vesciles travel to after the golgi?
Cytoplasm
what type of gland is the pancreas?
both endocrine and exocrine
what group of cells make up the endocrine pancreas?
islets of langerhans
3 cells of islets of langerhans
alpha beta gamma
what cells make up the exocrine pancreas?
secretory acini
what 2 enzymes are released by the acini cells
- chymotrysinogen
- trypsinogen
what is a zymogen?
inactive substance which is coverted to an enzyme by another enzyme
which organ conducts protein synthesis?
Ribsomes on rough ER
how do secretory proteins enter the ER lumen to segregate from the cytosolic proteins?
via signal recognition proteins (SRPs)
how are proteins processed?
glycosylation
when are proteins exocytosed?
when ligands bind to the cell membrane
2 causes of disease:
1) genetics
2) environment
what is multifactorial inheritance?
phenotype determined by multiple genes at multiple loci
which has a higher penetrance, monogenic or polygenic diseases?
monogenic
which disease type can have gene predisposition and environmental contribution?
polygenic
what does it mean if a disease is fully penetrant?
other genes or the environment doesnt affect it
In the threshhold model, the frequency of distribution is being measured between who?
relatives vs the general population
what are epistatic alleles?
only have an effect if in conjuction with another mutation
what disease is strongly influenced by genes?
autism
what does SNP stand for?
single nucleotide polymorphism
what is a SNP?
point mutation occuring in the same place (gene) in another chromosome
chromosomal deletion syndrome?q
DiGeorge syndrome
what are autosomal diseases?
not affecting sex chromosomes
term that describes, ‘different mutations in the same gene cause different diseases’
genetic heterogenecity
what is prophylaxis?
treatment given to prevent disease
another word for pharmacogenomics?
precision medicine
what is pharmacogenomics
correlating gene expression from SNPs with a drugs efficacy/toxicity
advantages of precision medicine
- max efficacy
- minimal ADR
what does the process of pharmacogenomics measure?
polymorphisms in cytochrome P450
what is a genome
someones complete set of data
what is a nonsynomous mutation
a mutation that results in change in protein structure
what is gene therapy
replacing bad genes with good genes
2 types of gene therapy
- germline
2. somatic
which gene therapy only affects the individual?
somatic
definition of transgene delivery
genetic material which has been transferred naturally or by genetic engineering techniques from one organism to another
what does en vivo mean
outside of the bodyq
which type of gene therapy involves a delivery vehicle?
en vivo
what is the adenovirus?
common cold
what is the herpesvirus?
cold sore
what is the retrovirus?
HIV
which virus carries the DNA in the virion?
Herpesvirus
what virus carries RNA + Reverse transcriptase?
Retrovirus
which is the only virus to use its own transcription mechanism?
Retrovirus
