gene expression Flashcards
mutations, regulation of transciption&translation, epigenetics
gene mutation =
change in the DNA base seq. of a gene
when do gene mutations occur?
randomly during replication (interphase)
what increases the freq of gene mutations?
mutagenic agents
how can a gene mutation result in a non-functioning protein?
- change in a.a seq so change in primary struc
- H-bonds & ionic bonds will form in diff places
- change in tertiary struc
(diff shape so diff/non function)
how many types of mutation are there?
6
mutation
addition
- causes frame-shift to right
- all subsequent codons altered
- codes for diff a.a seq
mutation
deletion
- causes frame shift to left
- codes for diff a.a seq
mutation
substitution
- genetic code = degenerate –> new codon may still code for same a.a
- mutation may occur in intron –> a.a seq not affected
mutation
inversion
- section of bases –> inverted
- codes for diff a.a seq
mutation
duplication
- one particular base duplicated at least once
- causes frame shift to right
- codes for diff a.a seq
mutation
translocation
- a section of bases on one chromosome detaches and attaches onto another chromosome
- results in substantial alteration
- can cause signif impacts on gene exp.
stem cells =
undifferentiated cells that can continually divide and become specialised
types of stem cells
(all have diff differentiation abilities)
- totipotent
- pluripotent
- multipotent
- unipotent
2 uses of stem cell therapy
- produce tissues/organs for transplants
- treat irreversible diseases eg. heart disease
totipotent
- can divide to prod any type of body cell
- occurs only for limited time in early mammalian embryos
pluripotent
- can divide into unlimited numbers
- used to treat human disorders
- found in embryos
multipotent & unipotent
- can divide to form a limited no. of diff cell types
- found in mature mammals
what are unipotent stem cells used to make?
cardiomyocytes
induced pluripotent cells
- prod from adult somatic cells –> overcomes ethical issues of using embryo stem cells
(to do this, the genes that were switched off to make the cell specialised must be switched back on –> done via use of transcription factors)
what is ‘controlling gene expression’?
either activating or inhibiting a gene
example of activating genes
(initiating transcription)
using oestrogen
example of inhibiting genes
(inhibiting transcription)
using siRNA to inhibit the translation of mRNA
transcription factors
- transcription only occurs when a protein from the cytoplasm enters the nucleus and binds to the DNA in the nucleus –> protein = transcription factor
- initiates transcription of genes –> creates mRNA for that gene which can be translated in the cytoplasm
without binding of transcription factor, gene is inactive/not expressed
oestrogen
initiates transcription
1. steroid hormone so it diffuses through cell membrane –> lipid soluble
2. binds to receptor site on transcription factor –> causes shape to change slightly
3. change in shape makes it comple. to DNA –> thus, binds to DNA
epigenetics =
the heritable change in gene function, without changing the DNA base seq
(changes caused by change in environment)
name the methods of inhibiting transcription via epigenetics
- increased methylation of DNA
- decreased acetylation of histone proteins
(doing the opposite would initiate transcription)
increased methylation of DNA
- methyl groups attach to cytosine bases in DNA
- prevents transcription factors from binding to DNA
- causes nucleosomes to pack tightly together
- gene will not be expressed
(inhibits transcription)
decreased acetylation of histone proteins
- histone acetylation results in loose packing of nucleosomes
- if acetyl groups removed, histones become more positive –> more attr to phosphate on the DNA –> DNA & histones more strongly associated
- prevents transcription factors from binding to DNA
- gene will not be expressed
(inhibits transcription)
what is RNA interference? (RNAi)
(only for eukaryotes and SOME prokaryotes)
- inhibits translation of mRNA prod from target genes
- an mRNA that has alr been transcribed is destroyed before translation
process of RNA interference (RNAi)
- an enzyme cuts the mRNA into siRNA
- one strand of the siRNA combines with another enzyme
- the siRNA-enzyme complex binds to another mRNA via comple base pairing
- once bound, the enzyme cuts up the mRNA –> cannot be translated –> gene inhibited
cancer =
results from mutations in genes that regulate mitosis –> uncontrolled cell division –> formation of malignant tumour
benign tumours
grow very large but at slow rate
1. non-cancerous –> prod adhesive molecules, sticking them together & to a particular tissue
2. often surrounded by capsule –> remain compact –> easily removed by surgery
3. impact = localised
4. not life-threatening
malignant tumours
cancerous & grow rapidly
1. cell nucleus grows large –> becomes unspecialised again
2. don’t prod the adhesive –> instead metastasise –> tumour breaks off & spreads to other tissues in the body
3. tumour not encapsulated –> instead grow projections into surrounding tissues –> grows its own blood supply
4. life-threatening –> recurrence also likely
3 causes of tumour development
- gene mutations in tumour suppressor genes & oncogenes
- abnormal methylation of TSGs & oncogenes
- increased oestrogen concs in the development of breast cancer
how do tumour supressor genes work?
prod proteins to slow down cell division & cause cell death if DNA copying errors detected
1
TSG mutations
- protein no longer prod./apoptosis occurs
- cell division continues
- mutated cells not identified & destroyed
1
oncogene mutations
- oncogene = mutated version of proto-oncogene which creates a protein involved in the initiation of DNA replication & cell division
- oncogene mutation –> causes process to be permanently activated –> makes cells divide continually
2
abnormal methylation of TSGs
- hypermethylation of TSGs
- transcription of TSGs inhibited/gene becomes inactivated
- protein no longer prod./apoptosis
- uncontrolled cell division
2
abnormal methylation of oncogenes
- hypomethylation of oncogenes
- gene becomes permanently activated
- continually produces protein which initiates DNA replication & cell division
3
increased oestrogen conc
- oestrogen can bind to a gene that initiates transcription, activating it
- if its a proto-oncogene, permanently activating it causes cells to continually divide
- increased oestrogen conc, increased chance of binding
when & where is oestrogen prod?
- prod by ovaries to regulate mentrual cycle –> stops after menopause
- fat tissues in breasts can prod oestrogen –> causes breast cancer post-menopause
