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OCR A Level Biology Your notes

6.1 Cellular Control

Contents
6.1.1 Gene Mutations
6.1.2 Gene Control
6.1.3 Gene Control: Lac Operon
6.1.4 Gene Control: Transcription Factors
6.1.5 Gene Control: Post-Transcriptional Modification
6.1.6 Gene Control: Body Plans
6.1.7 The Importance of Mitosis & Apoptosis

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6.1.1 Gene Mutations

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Gene Mutations & Their Effect on Polypeptides
A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an
altered polypeptide
Mutations occur continuously
Mutations can occur spontaneously (i.e. for no reason) during DNA replication
The probability of a mutation occurring can increase with the presence of certain factors known as
mutagens, e.g.
Ionising radiation such as X-rays can break the DNA strands which can then be altered during
the repair process
Deaminating chemicals can alter the chemical structure of bases, converting one base into
another
Methyl or ethyl groups can be added to bases, leading to incorrect base pairing
Viruses can insert sections of viral DNA into the DNA of cells
These mutations usually have no effect on us:
As most mutations do not alter the polypeptide or only alter it slightly so that its structure or
function is not changed (as the genetic code is degenerate i.e. several different triplets often
code for the same amino acid)
Many mutations occur in non-coding sections of DNA and so have no effect on the amino acid
sequence at all
However, a mutation in a gene can sometimes lead to a change in the polypeptide that the gene
codes for (as the DNA base sequence determines the sequence of amino acids that make up a protein)
There are three main ways that a mutation in the DNA base sequence can occur:
Insertion of one or more nucleotides
Deletion of one or more nucleotides
Substitution of one or more nucleotides
Insertion of nucleotides
A mutation that occurs when a nucleotide (with a new base) is randomly inserted into the DNA
sequence is known as an insertion mutation
An insertion mutation changes the amino acid that would have been coded for by the original base
triplet, as it creates a new, different triplet of bases
Remember – every group of three bases in a DNA sequence codes for an amino acid
An insertion mutation also has a knock-on effect by changing the triplets (groups of three bases)
further on in the DNA sequence
This is sometimes known as a frameshift mutation
This may dramatically change the amino acid sequence produced from this gene and therefore the
ability of the polypeptide to function

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Your notes

An example of an insertion mutation

Deletion of nucleotides
A mutation that occurs when a nucleotide (and therefore its base) is randomly deleted from the DNA
sequence
Like an insertion mutation, a deletion mutation changes the amino acid that would have been coded
for
Like an insertion mutation, a deletion mutation also has a knock-on effect by changing the groups of
three bases further on in the DNA sequence
Like an insertion mutation, this is sometimes known as a frameshift mutation
This may dramatically change the amino acid sequence produced from this gene and therefore the
ability of the polypeptide to function
Substitution of nucleotides
A mutation that occurs when a base in the DNA sequence is randomly swapped for a different base
Unlike an insertion or deletion mutation, a substitution mutation will only change the amino acid for the
triplet (a group of three bases) in which the mutation occurs; it will not have a knock-on effect
Substitution mutations can take three forms:
Silent mutations – the mutation does not alter the amino acid sequence of the polypeptide (this
is because certain codons may code for the same amino acid as the genetic code is degenerate)
Missense mutations – the mutation alters a single amino acid in the polypeptide chain (sickle cell
anaemia is an example of a disease caused by a single substitution mutation changing a single
amino acid in the sequence)
Nonsense mutations – the mutation creates a premature stop codon (signal for the cell to stop
translation of the mRNA molecule into an amino acid sequence), causing the polypeptide chain
produced to be incomplete and therefore affecting the final protein structure and function (cystic
fibrosis is an example of a disease caused by a nonsense mutation, although this is not always the
only cause)

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Your notes

An example of a substitution mutation

The effect of gene mutations on polypeptides
Based on the effect they have on an organism, gene mutations can be placed into one of three
categories:
Beneficial mutations
Harmful mutations
Neutral mutations
Beneficial mutations
A small number of mutations result in a significantly altered polypeptide with a different shape
This may alter the ability of the protein to perform its function. For example:
If the shape of the active site on an enzyme changes, the substrate may no longer be able to bind
to the active site
A structural protein (like collagen) may lose its strength if its shape changes
In some cases, this alteration to a polypeptide may actually result in an altered characteristic in an
organism that causes beneficial effects for the organism
In these cases, the original mutation is referred to as a beneficial mutation
An example of a beneficial mutation that occurred in humans involves the production of the pigment
melanin:
Early humans living in Africa had dark skin as they produced high concentrations of the pigment
melanin
This provided protection from harmful UV radiation from the Sun, whilst still allowing vitamin D to
be synthesised (due to the high sunlight intensity)
However, at lower sunlight intensities, pale skin synthesises vitamin D more easily than dark skin

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As humans moved into cooler temperate climates, certain mutations occurred that led to a
decrease in the production of melanin
These paler-skinned individuals would have had a selective advantage, as they could synthesis Your notes
more vitamin D (a lack of vitamin D causes a range of health problems, including rickets and
reduced protection against heart disease and cancers)
The mutations that led to a decrease in the production of melanin are therefore referred to as
beneficial mutations
Harmful mutations
By altering a polypeptide, some mutations can lead to an altered characteristic in an organism that
causes harmful effects for the organism
In these cases, the original mutation is referred to as a harmful mutation
Many genetic diseases are caused by these harmful mutations (e.g. haemophilia and sickle cell
anaemia)
An example of a harmful mutation that occurs in humans is that which causes cystic fibrosis:
In around 70% of cystic fibrosis sufferers, the mutation that causes this disease is a deletion
mutation of three nucleotides in the gene coding for the protein CFTR
The loss of function of the CFTR protein caused by this deletion mutation results in a number of
symptoms, including lung and pancreatic problems as a result of extremely thickened mucus
Neutral mutations
Neutral mutations offer no selective advantage or disadvantage to the individual organism
This can occur either because:
A mutation does not alter the polypeptide
A mutation only alters the polypeptide slightly so that its structure or function is not changed
A mutation alters the structure or function of the polypeptide but the resulting difference in the
characteristic of the organism provides no particular advantage or disadvantage to the organism
An example of a neutral mutation that occurs in humans involves the ability to taste a bitter-tasting
chemical that is found in Brussel sprouts:
This chemical is not toxic so it is not advantageous for us to be able to taste it
The ability to taste this chemical is caused by a mutated allele of the TAS2R38 gene
The TAS2R38 gene allows us to taste bitter things by coding for receptor proteins that can detect
bitter-tasting chemicals
However, the mutated allele of this gene causes an increased perception of bitterness, meaning
that people with this mutation can taste the bitter-tasting chemical in Brussel sprouts (whereas
people without the mutation cannot)
Although this is now seen as a neutral mutation, it may have been advantageous in the past for
humans to be able to detect these bitter-tasting chemicals, as large quantities of bitter
substances can be harmful and many poisons have a bitter taste

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Examiner Tip
Your notes
You may also have read about silent mutations, which is a type of neutral mutation. A silent mutation is a
change in the nucleotide sequence that results in the same amino acid sequence.This is possible
because some amino acids can be coded for by up to four different triplet codon sequences.Silent
mutations are often a change in the 2nd or 3rd base in the codon, rather than the first.For example, the
amino acid valine is coded for by four different triplet codon sequences (GUU, GUC, GUA and GUG) –
therefore, as long as the first two nucleotides in the codon are guanine and uracil, the amino acid valine
will be inserted into the polypeptide.

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6.1.2 Gene Control

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Gene Control
The nucleus of every cell in the human body contains the same genes
However, not every gene is expressed in every cell
In addition, not all of these genes are expressed all the time
There are several mechanisms that exist within cells to make sure the correct genes are expressed in
the correct cell at the correct time
These mechanisms are known as regulatory mechanisms
They control which genes are expressed at different points in time (e.g. during development)
There are three main types of regulatory mechanisms, including:
Regulation at the transcriptional level (i.e. regulatory mechanisms that occur during transcription)
Regulation at the post-transcriptional level (i.e. regulatory mechanisms that occur after
transcription)
Regulation at the post-translational level (i.e. regulatory mechanisms that occur after translation)
These regulatory mechanisms are controlled by many different regulatory genes
Structural and regulatory genes
A structural gene codes for a protein that has a function within a cell (e.g. enzymes, membrane
carriers, hormones etc.)
For example, the F8 gene codes for the protein Factor VIII involved in blood clotting
Regulatory genes code for proteins (or various forms of RNA) that control the expression of structural
genes

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6.1.3 Gene Control: Lac Operon

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Gene Control: Lac Operon
Regulatory genes control structural genes and their levels of protein production
Regulatory genes sometimes have control over several structural genes at once
If the structural genes being controlled are in any way involved in the process of transcription, then
gene control is occurring at the transcriptional level
The lac operon provides an example of a regulatory mechanism at the transcriptional level (i.e. a
regulatory mechanism that occurs during transcription)
The lac operon
Structural genes in prokaryotes can form an operon: a group or a cluster of genes that are controlled
by the same promoter
The lac operon found in some bacteria is one of the most well-known of these
The lac operon controls the production of the enzyme lactase (also called β-galactosidase) and two
other structural proteins
Lactase breaks down the substrate lactose so that it can be used as an energy source in the bacterial
cell
It is known as an inducible enzyme (this means it is only synthesized when lactose is present)
This helps prevent the bacteria from wasting energy and materials
Structure of the lac operon
The components of the lac operon are found in the following order:
Promoter for structural genes
Operator
Structural gene lacZ that codes for lactase
Structural gene lacY that codes for permease (allows lactose into the cell)
Structural gene lacA that codes for transacetylase
Located to the left (upstream) of the lac operon on the bacterium's DNA there is also the:
Promoter for regulatory gene
Regulatory gene lacI that codes for the lac repressor protein
The lac repressor protein has two binding sites that allow it to bind to the operator in the lac operon
and also to lactose (the effector molecule)
When it binds to the operator it prevents the transcription of the structural genes as RNA
polymerase cannot attach to the promoter
When it binds to lactose the shape of the repressor protein distorts and it can no longer bind to
the operator

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Your notes

The components of the lac operon along with the upstream regulatory gene and its associated
promoter
When lactose is absent
The following processes take place when lactose is absent in the medium that the bacterium is
growing in:
The regulatory gene is transcribed and translated to produce lac repressor protein
The lac repressor protein binds to the operator region upstream of lacZ
Due to the presence of the repressor protein RNA polymerase is unable to bind to the promoter
region
Transcription of the structural genes does not take place
No lactase enzyme is synthesized

The repressor protein binding to the operator region of the lac operon and preventing transcription of
the structural gene
When lactose is present
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The following processes take place when lactose is present in the medium that the bacterium is
growing in:
There is an uptake of lactose by the bacterium Your notes
The lactose binds to the second binding site on the repressor protein, distorting its shape so that
it cannot bind to the operator site
RNA polymerase is then able to bind to the promoter region and transcription takes place
The mRNA from all three structural genes is translated
Enzyme lactase is produced and lactose can be broken down and used for energy by the
bacterium

The binding of lactose to the repressor protein frees up the operator region of the lac operon so RNA
polymerase can bind and begin transcription of the structural genes

Examiner Tip
The example above explains how the genetic control of an inducible enzyme works.However, you
could get some questions on the genetic control of repressible enzymes.In this mechanism, an
effector molecule also binds to a repressor protein produced by a regulatory gene. However this
binding actually helps the repressor bind to the operator region and prevent transcription of the
structural genes. So it's the opposite of the lac operon: when there is less of the effector molecule,
the repressor protein cannot bind to the operator region and transcription of the structural genes
goes ahead, meaning the enzyme is produced.

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6.1.4 Gene Control: Transcription Factors

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Gene Control: Transcription Factors
Eukaryotes can use transcription factors to control gene expression
Transcription factors are proteins that bind to specific regions of DNA to control the transcription
of genes
It is estimated that ~10% of human genes code for transcription factors
There are several types of transcription factors that have varying effects on gene expression
This is still a relatively young area of research and scientists are working hard to understand how all
the different transcription factors function
Transcription factors allow organisms to respond to their environment
Some hormones achieve their effect via transcription factors
How transcription factors work
Some transcription factors bind to the promoter region of a gene (i.e. the region of DNA 'upstream' of
the gene that controls the expression of the gene)
This binding can either allow or prevent the transcription of the gene from taking place
The presence of a transcription factor will either increase or decrease the rate of transcription of a
gene

A transcription factor binding to the promoter region of a gene which allows RNA polymerase to bind
and for transcription to occur
Gene control: oestrogen
In mammals, the hormone oestrogen is involved in controlling the oestrus cycle and also in sperm
production
Oestrogen is a lipid-soluble molecule and can therefore diffuse through the plasma membrane of
cells
It then moves to the nucleus and binds to an oestrogen receptor

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These receptors are actually transcription factors that are able to initiate transcription for many
different genes by binding to their promoter regions
Once bound, oestrogen causes a change in the shape of the receptor Your notes
As a result, the receptor moves away from the protein complex it is normally attached to and binds to
the promoter region of one of its target genes
This allows RNA polymerase to bind and to begin transcribing that gene

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Your notes

A summary of how oestrogen can stimulate the transcription of a gene

Gene control: gibberellin
Plant cells use transcription factors in a similar way to animal cells
Gibberellin is a hormone found in plants (e.g. wheat and barley) that controls seed germination by
stimulating the synthesis of the enzyme amylase
It does this by influencing transcription of the amylase gene
When gibberellin is applied to a germinating seed there is an increased amount of the mRNA for
amylase present
Mechanism
The breakdown of DELLA protein by gibberellin is necessary for the synthesis of amylase
The following components are involved:
Repressor protein DELLA
Transcription factor (the one involved is called PIF)
Promoter of amylase gene
Amylase gene
Gibberellin
Gibberellin receptor and enzyme
The process occurs as follows:
DELLA protein is bound to the transcription factor, preventing it from binding to the promoter of the
amylase gene so no transcription can occur
Gibberellin binds to a gibberellin receptor and enzyme which starts the breakdown of DELLA
The transcription factor is no longer bound to DELLA protein and so it binds to the promoter of the
amylase gene
Transcription of amylase gene begins
Amylase is produced

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Your notes

The breakdown of DELLA protein by gibberellin allows the transcription factor PIF to bind to the
promoter for the amylase gene and for transcription to initiate

Examiner Tip
In your exam you may be asked to explain why RNA analysis is important with regards to gene
expression. From the outside most cells look almost identical with the same DNA in their nucleus.
However we know that they are most likely expressing different genes.When a cell expresses a gene,
RNA is produced by transcription. This RNA present in a cell can be analysed. Scientists can match the
RNA present in a cell to specific genes and work out which genes are being expressed in that specific
cell.
You are not required to recall specific transcription factors for your exam.

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6.1.5 Gene Control: Post-Transcriptional Modification

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Post-Transcriptional Modification
Within eukaryotic genes, there are both coding and non-coding sequences of DNA
The coding sequences are called exons and these are the sequences that will eventually be
translated into the amino acids that will form the final polypeptide
The non-coding sequences are called introns and are not translated (they do not code for any
amino acids)
When transcription of a gene occurs, both the exons and introns are transcribed
This means the messenger RNA (mRNA) molecule formed also contains exons and introns
This RNA molecule is often referred to as primary mRNA or pre-mRNA
As the introns are not to be translated, they must be removed from the pre-mRNA molecule
The exons are then all fused together to form a continuous mRNA molecule called mature mRNA that is
ready to be translated
This process is sometimes called ‘splicing’ and is part of the process of post-transcriptional
modification (referring to the modification of the RNA molecule after transcription but before
translation occurs)
Splicing ensures that only the coding sections of mRNA are used to form proteins by translation (if any
introns were included in the mature mRNA, the resulting protein would not be formed properly and may
not function as it should)

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Your notes

The RNA molecule (known as pre-mRNA) produced from the transcription of a gene contains introns
that must be removed (to form mature mRNA) before translation can occur
Control at the post-translational level
After polypeptides are formed by translation, they undergo modifications in the Golgi apparatus or in
the cytosol
Some polypeptides may then require activation by cyclic AMP (also known as cAMP)
cAMP is derived from ATP and is formed by the action of the enzyme adenyl cyclase
One important role carried out by cAMP is the activation of protein kinases
In eukaryotic cells, cAMP activates protein kinase A (also known as PKA)
PKA is an inactive precursor enzyme
Once it is activated, it can activate other proteins (e.g. other enzymes)
For example, when muscle cells require energy, an enzyme called glycogen phosphorylase releases
glucose from glycogen
This enzyme is activated by cAMP, which changes the shape of the enzyme to expose its active site

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6.1.6 Gene Control: Body Plans

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Body Plans & Hox Genes
Cells in developing organisms need to be able to differentiate and specialise for different roles
In order to do this, they must be able to control which genes are functioning at a particular time
This is achieved by 'switching on' and 'switching off' genes
This must occur in a specific, tightly controlled sequence
This sequence is determined by transcription factors (proteins that bind to specific DNA
sequences in order to control the rate at which particular genes are transcribed into mRNA)
Homeobox genes
A homeobox is a DNA sequence that codes for a protein transcription factor
The transcription factors (that homeobox sequences code for) attach to DNA at specific locations
and regulate the transcription of genes (e.g. genes that control the early development of
eukaryotic organisms) by turning various different genes on and off in the correct order
A homeobox gene is any gene that contains a homeobox sequence
Homeobox gene sequences in plants, animals and fungi are similar and highly conserved (meaning
they have been maintained by natural selection i.e. they remain relatively unchanged when travelling
back in evolutionary time)
The sequences are all similar as they all code for amino acid sequences that will form transcription
factors, the DNA-binding regions of which must all have the same shape
Mutations that cause changes in these homeobox sequences can lead to organisms that are not
viable (not properly developed) so they are not favoured by natural selection. This strong
negative selection pressure explains why the sequences are highly conserved
Homeobox genes are responsible for the genetic control of the development of body plans in
different organisms
This means they help to form the basic pattern of the body
For example, they control the polarity of the organism (which end will develop into the head and
which end will develop into the tail)
They also control the segmentation of organisms such as insects and mammals into distinct body
parts and they control the development of body parts such as wings and limbs, as well as what
organs are present in each section of the body
In this way, homeobox genes can be seen as 'master genes' that control which genes function at
different stages of development

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Your notes

Eight homeobox genes (specifically, Hox genes) of the fruit fly, Drosophila melanogaster, that control
the development of the body plan into specific regions e.g. the head, thorax, and abdomen. The break
mark (//) in the chromosome shows that these are two clusters of genes that are separated by a long
intervening region of the chromosome that is not shown here
Hox genes
Hox genes are a very important subset of homeobox genes
They determine the identity of embryonic body regions along the anterior-posterior axis (i.e. the
head-tail axis)
These Hox genes are organised into groups known as Hox clusters
Vertebrates have four Hox clusters (each containing 9-11 Hox genes), which are found on different
chromosomes
There is a linear order to the Hox genes in each Hox cluster and this order is directly related to the
order of the regions of the body that they affect

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Your notes

The four Hox clusters containing the Hox genes that control the development of the body plan of
vertebrates into specific regions

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6.1.7 The Importance of Mitosis & Apoptosis

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The Importance of Mitosis & Apoptosis
Mitosis is the type of cell division that produces identical new cells for processes such as growth, cell
replacement and tissue repair
Apoptosis is programmed cell death (sometimes referred to as natural cell death)
In apoptosis, old cells that have already undergone a large number of mitotic cell divisions
(approximately 50 divisions, although this depends on the cell type) are systematically taken through
various processes leading to cell death
These processes include:
The DNA of the cell becoming denser and more tightly packed
The nuclear envelope of the cell's nucleus breaking down and chromatin condensing
Vesicles forming that contain hydrolytic enzymes
Phagocytes engulfing and digesting the cell via phagocytosis
The importance of mitosis and apoptosis in controlling body plan development
By constantly replacing and destroying cells throughout the early development of an organism,
mitosis and apoptosis are both key mechanisms controlling the development of body form
Apoptosis is important in development as, in some cases, some cells that are produced (by mitosis)
earlier on in development may no longer be needed
As a result, these cells are destroyed (by apoptosis) as part of the development of the organism
For example, structures like fingers and toes first develop as a single combined unit and are then
separated later via programmed cell death (apoptosis) of the cells in between the digits
The control of mitosis and apoptosis
Mitosis is controlled by various different genes that are categorised into two distinct groups:
Proto-oncogenes are genes that stimulate cell division
Tumour-suppressor genes are genes that reduce cell division
Tumour-suppressor genes can also stimulate apoptosis in cells with damaged DNA that cannot be
repaired
This protects the body as it ensures that any cells that are genetically damaged (and that could,
therefore, lead to cancer) are destroyed
During the cell cycle (in cells due to undergo mitosis) there are various 'checkpoints' that need to be
passed to ensure that damaged cells are not produced
These controls ensure that the cell is prepared for the mitosis phase of its cell cycle and that any DNA
damage is repaired
These controls are regulated by two groups of proteins, known as cyclins and cyclin-dependent
kinases (CDKs), that regulate the progress of the cell through the cell cycle
Cyclins act as regulators
CDKs act as catalysts (once activated by cyclins)

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For example, CDKs that have been activated by cyclins will catalyse the phosphorylation of
particular target proteins, which can either activate or inactivate them
This ensures the cell cycle progresses from one stage to the next Your notes
Different cyclins are produced at different stages of the cell cycle in response to internal
molecular signals
The genes that control the cell cycle and apoptosis are able to respond to:
Internal cell stimuli
External cell stimuli
Examples of internal cell stimuli
Internal factors that affect apoptosis and the cell cycle include:
Irreparable genetic damage
RNA decay
Internal biochemical changes that lead to cell changes or cellular injury (e.g. oxidative reactions)
Production of cyclin D
These factors can all initiate apoptosis in cells
Examples of external cell stimuli
External factors that affect apoptosis and the cell cycle include:
The presence of cell signalling molecules such as cytokines from the immune system, hormones
and growth factors
Viruses and bacteria, harmful pollutants or ultraviolet light can affect the delicate balance of
mitosis and apoptosis by damaging or destroying cells faster than they can be repaired or
replaced
Cells often respond to such stressful stimuli by activating pathways to increase their chance of
survival, or by initiating apoptosis

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