control of gene expression Flashcards
substitution
one or more bases swapped for another
deletion
one or more bases removed
addition
one or more bases added
duplication
one or more bases repeated
inversion
a sequence of bases is reversed
translocation
sequence of bases moved from one location in genome to another
(could be within same or different chromosomes)
when do gene mutations occur?
spontaneously during DNA replication
mutagenic agents increase the rate of mutation
effects of mutations
different amino acid sequence made in polypeptide
change in sequence may change tertiary structure of protein
could stop it functioning
eg if its an enzyme, active site won’t be complementary shape to substrate
what does degenerate mean? and its impact on mutations
some amino acids coded for by more than one DNA triplet
means not all mutations change amino acid sequence
what is a frame shift?
happens due to mutations
- often addition, duplication and deletions
happens as they change the number of bases in a DNA code
changes nature of all base triplets that follow, code read in a different way
- affects amino acid sequence
examples of mutagenic agents
UV radiation
ionising radiation
chemicals
how can mutagenic agents increase rate or mutations? (3)
act as a base
- substitute for a base
- causes substitution mutations
- changes base sequence
alter a base
- can delete or alter bases
- changes sequence
changing DNA structure
- causes issues in replication
- increases likelihood of mutations
causes of cancer
when mutations happen in genes that control cell division
- tumour supressor genes
- proto-oncogenes
causes uncontrolled cell growth
results in tumour
- mass of abnormal cells which invade and destroy surrounding tissue
malignant tumours
cancers
- grow rapidly
- invade and destroy surrounding tissue
- cells can break off and spread in bloodstream
benign tumours
not cancerous
- grow slower
- covered in fibrous tissues, stops invading
- often harmless, can become malignant
what do tumour cells look like?
- irregular shape
- larger and darker nucleus
- different antigens
- divide more frequently (don’t respond to regulating processes)
role of tumour suppressor genes
working normally:
- slow cell division
- produce proteins to stop cell division or to make cells self destruct
can be inactivated by a mutation:
- doesn’t produce protein to slow division
- stimulates cells divide uncontrollably = tumour
role of proto-oncogenes
working normally:
- stimulate cell division
- produces proteins to make cell divide
effect can be increased due to mutation:
- gene becomes overactive
- stimulates cells to divide uncontrollably = tumour
what are oncogenes?
Mutated proto oncogene
caused by hypomethylation
what is methylation?
adding a methyl group
methylation of DNA controls weather or not the DNA is transcribed and translated
abnormal methylation is when it happens to much or too little
- hypomethylation
- hypermethylation
how can abnormal methylation cause tumours?
- hypermethylation of tumour - suppressor genes
- gene isn’t transcribed
- protein to slow division not made
- divide uncontrollably = tumour
- hypomethlyation of proto-oncogenes
- act as oncogenes
- increases amount of proteins that stimulate cell division
- divide uncontrollably = tumour
how does oestrogen cause cancer?
increased exposure over long periods of time - increased risk of breast cancer
- can stimulate certain breast cells to divide
more cell division taking place increases chance of mutations and cells becoming cancerous - the ability to stimulate division mean any cancerous cells would be able to divide even faster
tumour form more quickly - may be able to introduce mutations directly in DNA causing mutations
2 types of risk factors
something that increases someones chance of developing cancer
genetic - linked to specific inherited alleles - if inherited, more at risk
environmental - exposure to radiation, smoking, increased alcohol and fat diet increase risk
how can understanding roles of the genes be used in prevention?
if a specific mutation causing cancer is known, it can be screened for
knowing this risk can allow for prevention
- screened more often
- lifestyle choices
increased recovery when found early
knowing genes can also mean better tests for cancers
- easier and more accurate diagnosis
how can understanding roles of the genes be used in treatment and cures?
treatments are different for different mutations
- allows for more specific treatments to be made
- more effective in targeting it
- more treatment (eg higher doses) can be used for more aggressive cancers caused by different mutations
gene therapy - replace faulty genes with working ones
knowing which gene cause the cancers can also them be to changed
what are stem cells?
unspecialised cells that can differentiate into other types of cell
what are totipotent cells?
stem cells that can divide and produce any type of body cell
only translate part of their DNA, allowing them to become specialised
only present in mammals in first few divisions of embryo
- then become pluripotent
what are pluripotent cells?
found in embryos
can specialise into any cell but ones that make up placenta
multipotent stem cells
found in adult mammals
able to differentiate into few types of cell
eg red and white blood cells from bone marrow
unipotent stem cells
only differentiate into one type of cell
found in adult mammals
how to stem cells become specialised?
only transcribe and translate part of their DNA
all contain same genes
due to conditions, some genes are expressed and other switched off
mRNA only transcribed from specific genes so only specific proteins made in translation
proteins modify cell eg structure
= specialised
unipotent cells in the heart
cardiomyocytes - heart muscle cells
thought that heart cells couldn’t be regenerated (issue if damaged)
now thought there is small supply of unipotent stem cells in heart
- specials to replace damaged cells
use of pluripotent stem cells in treating disorders
as they can specialise into any type of cell, can be used to replace damaged cells
- bone marrow contains stem cells that can specialise into any blood cell
- bone marrow transplants are used to replace faulty bone marrow in patents with abnormal blood cells
- cells in transplant divide and specialise into healthy blood cells
eg leukaemia
sources of stem cells
adult stem cells - body tissues of adult
eg bone marrow
obtained in simple operation
but not as flexible - multipotent (a few types)
embryonic stem cells - embryos in early stages of development
created in lab using in vitro fertilisation (outside of womb)
stem cells remove and embryo destroyed
pluripotent - any number of any cell
iPS cells
what are iPS cells?
induced pluripotent stem cells
created in a lab
reprogramming specialised adult body cells to become pluripotent
- made to express transcription factors associated with pluripotent cells
- cause there body cells to express genes associated with the stem cells
will be useful in medicine and ethical (see benefits of stem cells)
how are iPS cells made?
made to express transcription factors to make them express genes associated with pluripotent stem cells
- infect with specific modified virus
- virus has genes coding for transcription factors in its DNA
- when it infects, genes passed on to adult cells DNA, cell produces transcription factors
benefits of stem cell treatments
save many lives
eg those waiting for transplants, new organs made from stem cells to reduce waiting
improve quality of life
replace damaged cells eg blindness
iPS cells are from adult stem cells - more ethical
but can still specialise into any cell
iPS made from patients cells - genetically identical
less chance of rejection
issues of using stem cells treatments
ethical issues of using embryonic stem cells
- results in destruction of embryo, could become fetus
- less objection to those from egg cells that haven’t been fertilised, wouldn’t become fetus
should use adult stem cells - doesn’t destroy embryo
but can’t specialise into any cell
why do cells have different functions?
cells in an organism all have the same genes
but structure and function varies as not all genes are expressed (transcribed and translated)
different genes expressed = different proteins made, determine structure and processes
what are transcription factors?
proteins that control whether or not genes are transcribed
bind to promotor reigons upstream of gene
promotor region
section of DNA upstream of a gene
binding site for transcription factors
how do transcription factors work?
control expression by controlling rate of transcription
not transcribed = not expressed
- move from cytoplasm to the nucleus, through pores
- bind to promotor region (upstream of the gene they control the expression of)
activators - stimulate or increase rate of transcription
help RNA polymerase bind to start of target gene = activate transcription
repressors - inhibit or decrease rate of transcription
prevent RNA polymerase from binding = inhibited
how does oestrogen initiate transcription?
oestrogen is a steroid hormone
affects transcription
- diffuses into cells through phospholipid bilayer (lipid soluble)
- binds to complementary site on transcription factor (oestrogen receptor)
- forms an oestrogen - oestrogen receptor complex
complex changes shape
- moves from cytoplasm to nucleus, thorugh nuclear pores
binds to specific base sequence near start of target gene (promoter)
complex acts as an activator
helps RNA polymerase bind
initiates transcription
what is a steroid hormone? (oestrogen)
small and lipid soluble
can diffuse directly through membrane
what is RNA interference? (RNAi)
where small, double stranded RNA molecules (non-coding) stop mRNA from target genes being translated into proteins
also affects gene expression (inhibits)
done by siRNA (small interfering)
or miRNA (micro)
how is siRNA made?
DNA transcribed and replication = Double stranded RNA
Broken up by enzymes into double stranded siRNA
DICER, hydrolyses
Hydrogen bonds broken
Joined to enzyme (eg RISC)
Creates siRNA
how does siRNA work in mammals? (miRNA in plants)
DNA transcribed and replicated
= double stranded RNA
broken up by enzymes into pieces
(eg DICER)
hydrogen bonds broken
= single stranded siRNA
associates with enzyme
(eg RISC)
in cytoplasm:
siRNA then binds to target mRNA
- base sequence of siRNA complementary to base sequence of target mRNA
Enzyme with siRNA, cut the mRNA into fragments
- can’t be translated
fragments move to processing body where they are degraded
how does miRNA work?
miRNA not always complementary to target mRNA
- is less specific than siRNA, can target more than one mRNA molecule
miRNA associates with enzymes and binds to target mRNA in cytoplasm
miRNA - protein complex blocks the translation of target mRNA
mRNA then moved into processing body and stored or degraded
(stored to be translated later)
what is epigenetic control? (+ how it works)
determines whether or not a gene is expressed (transcribed and translated)
changes gene function without changing base sequence
works by attachment or removal of chemical groups - epigenetic marks
to or from DNA or histones
- changes how easy it is for machinery to interact
heritable
- changes due to changes in environment eg stress
reversible
types of epigenetic changes (2)
increased methylation of DNA
decreased acetylation of histones
= genes not expressed
inheritance of epigenetic marks
organisms inherit DNA base sequence from parents
some epigenetic marks are passed on to offspring (most removed)
means expression of some gene in offspring affected by environmental changes that impacted their parents
how does increased methylation inhibit transcription?
methyl group (epigenetic mark) is attached to the DNA coding for a gene
attaches at a CpG site
(where cytosine and guanine are joined by a phosphodiester bond)
increased methylation changes the DNA structure
transcriptional machinery can’t interact (eg enzymes)
gene isn’t transcribed (not expressed)
how does decreased acetylation inhibit transcription?
DNA wraps around histones to make chromatin
can be highly or less condensed due to presence of acetyl groups (epigenetic marks)
histones can be acetylated - add acetyl group
- makes chromatin less condensed
- DNA more accessible to machinery
- can be transcribed
acetyl groups can be removed from histones
- chromatin highly condensed
- genes in DNA less accessible, machinery can reach it
- not transcribed
histone deacetylase (HDAC) responsible for removing acetyl group
how does epigenetics lead to development of disease?
methylation controls which genes are expressed
abnormal methylation of certain genes can result in cancers:
hypermethylation of tumour suppressor genes
hypomethylation of proto-oncogenes
controls which genes are expressed, lead to uncontrolled cell growth
(decreased acetylation of tumour suppressor
increased acetylation of proto oncogenes)
how can drugs treat epigenetic changes?
epigenetic changes are reversible
drugs designed to counteract epigenetic changes
increased methylation = gene switched off
drugs can stop DNA methylation so gene still expressed
decrease acetylation = gene switched off
drugs can inhibit histone deacetylase (which remove the acetyl group) so genes remain acetylated, can be expressed
but drugs must be specific as epigenetic changes can happen naturally, must target right cells
epigenetic cancer treatment
removal of methyl groups from tumour suppressor genes
- allows them to be expressed = division slowed
removal of acetyl groups from histones of oncogenes
- more condensed = can’t be transcribed, division slowed
Pre transcriptional control
Transcription factors
Increased or decrease transcription
Post transcriptional control
RNA interference
Stop translation
development of a tumour
tumour supressor genes mutated or silenced
- mutations = inactive
- silenced - epigenetics/RNAi
proto oncogenes = oncogenes
- mutations = over active
- not switched off (hypomethylation, increased acetylation)
