Biochemistry and Molecular Biology solutions

Question 1

Which of the following is not true about antibody structure?

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Correct answer:

1. c) Antibodies are always secreted and function away from the cell. They are not attached to the cell membrane.

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All antibody units are made up of two identical heavy chains and two identical light chains. The Y shaped antibody unit has an antigen binding site at the end of each arm of the Y so all antibody units have at least two antigen binding sites. Those antibodies which are polymers of antibody units (IgM and secreted IgA) have more than two. The antigen binding sites within an antibody are derived from the interaction of identical light and heavy chains so they are identical. There are nine alternative genes coding for the constant region of the heavy chain. The class of antibody produced is determined by which one of these is expressed. There are just two types of light chain, either of which can occur in any class of antibody. Non-activated B-cells carry a sample of the antibody they are capable of secreting attached to their cell membrane. Additionally IgE functions attached to the membrane of the mast cell forming an antigen receptor for that cell.
Page reference: 495, 496, 497

Question 2

Where do precursor T-lymphocytes develop into fully competent but not yet activated T-cells?

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Correct answer:

1. a) The thymus gland

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Lymphoid stem cells derived from the bone marrow develop into competent T-lymphocytes, with a functioning T-cell receptor and co-receptor, in the thymus gland. Mature competent lymphocytes can also develop in the bone marrow, but these become B-cells capable of producing antibody molecules. Mature but non-activated lymphocytes leave these two primary lymphoid tissues and enter the blood and lymph, where they remain inactive until they encounter an antigen they recognize, presented by an antigen presenting cell. This happens in secondary lymphoid tissues, which include the lymph nodes and the white pulp areas of the spleen, as well as the mucosal associated lymphoid tissues of the gut and airways.
Page reference: 494

Question 3

Which of the following is not a feature of a secondary immune response to an antigen, when compared to the first response to the same antigen?

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Correct answer:

1. d) Antibody is generated without T-cell help.

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After the first response to an antigen the lymphocyte circulation contains many memory cells displaying antibody specific for that antigen. Therefore on a second encounter specific lymphocytes are located more quickly and in greater numbers than they were first time, so antibody production starts more quickly and much more antibody is produced. As the immune response progresses the amount of antigen displayed by antigen presenting cells decreases, creating competition for binding between B-cells, which ensures that only those producing a high affinity antibody are selected and survive. Thus the antigen binding affinity of the antibody produced increases. This is aided by mutation within the antibody gene in activated B-cells, primarily affecting the antigen binding regions. B-cell activation in the secondary immune response requires T-cell help, exactly as it does in the primary response.
Page reference: 497-9

Question 4

What is the normal immunological role of the CD8+ve T-cell

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Correct answer:

1. b) Kills virus infected cells.

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A CD8+ve (cytotoxic)T-cell recognizes small peptides derived from viral proteins being synthesized within an infected cell, and presented on the cell surface attached to a class I MHC antigen. It kills the infected cell, interrupting the virus life cycle. A CD4+ve (helper) T-cell recognizes peptides derived from antigens and presented on B-cell surfaces attached to class II MHC antigens. It stimulates the B-cell to develop into an antibody secreting plasma cell. Cytotoxic T-cells, helper T-cells and antibodies can all play a part in rejecting transplanted tissue, but this cannot be regarded as their normal immunological role since a tissue transplant is physiologically abnormal.
Page reference: 499 -501

Question 5

Cancer cells often have reduced amounts of cell surface proteins, including class I MHC antigens. Which of the following cells of the immune system can exploit this property to kill cancer cells?

Your answer:

1. d) Macrophages

Correct answer:

1. b) Natural killer cells

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Natural killer cells are lymphocytes which do not carry a specific antigen receptor (antibody or T-cell receptor) on their surface. Instead they recognize cells which express a lowered amount of MHC class I antigen, and they mount a cytotoxic attack against such cells. These cells may be virus infected, because some viruses attempt to avoid cytotoxic T-cell attack by suppressing expression of class I MHC antigen by the cells they infect, or they may be cancer cells. Cytotoxic T-cells kill virus infected cells but recognize viral peptides presented on the cell surface by class I MHC proteins. Helper T-cells recognize cells carrying foreign peptides presented by class II MHC proteins, and they stimulate the cells they recognize. Macrophages, the tissue based phagocytes, recognize pathogen specific surface molecules, and apoptotic cells, but do not recognize live tumour cells.
Page reference: 502

 

 

 

Question 1

Which of the following statements about the lipid constituents of membranes is correct?

Your answer:

1. a) Lateral movement of membrane lipids is catalysed by special proteins.

Correct answer:

1. c) Lateral movement of membrane lipids occurs rapidly within the plane of the bilayer.

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There are many different types of membrane lipids that make up lipid bilayers. Different cell types have different membrane composition as do membranes of organelles within a single cell. The inner and outer halves of the lipid bilayer of a membrane are often different and this asymmetry is preserved. Transverse movement of the lipids that make up the bilayer (colloquially known as flip-flop) is severely restricted; such movement would involve transferring the polar heads through the central hydrophobic hydrocarbon layer to get to the other side. This is energetically unfavourable. There are proteins that catalyse energy-dependent membrane flip-flop to maintain the asymmetry. Membrane lipids are able to move laterally and rapidly within the plane of the bilayer.
Page reference: Page 105

Question 2

Which of the following statements about membrane fluidity is correct?

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Correct answer:

1. c) Membrane fluidity is increased when there is a high proportion of cis unsaturated fatty acids in the glycerophosphate molecules that make up the bilayer.

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The fluidity of a membrane is mainly dependent on the type of fatty acids in its polar lipid molecules. In a glycerophosphate molecule the fatty acid attached to the C-1 -OH group of the glycerol is usually saturated while the one attached to the C-2 -OH group is unsaturated. Saturated fatty acids have straight chains. The chains of naturally occurring (cis isomers) unsaturated fatty acids are kinked. The latter do not pack as closely in the bilayer so the membranes remain fluid at lower temperatures. Unsaturated fatty acid tails reduce the temperature at which the bilayer loses its fluidity. This is important since membrane fluidity is essential to allow the lateral movement of transmembrane proteins in the membrane so that they can interact with one another. In addition the fluidity is essential for the conformational changes that occur when those proteins function as ion channels, transporters or receptors.
Page reference: Page 106

Question 3

Which of the following statements about membrane proteins is not correct?

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Correct answer:

1. b) Integral membrane proteins are anchored to the lipid bilayer by ionic bonds.

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Many different types of membrane proteins are essential for the functions of a cell. They can transfer information or allow the controlled transport of molecules via conformational changes. Integral membrane proteins have hydrophilic terminal ends and hydrophobic centres. The transmembrane domains of integral membrane proteins can be single or multiple hydrophobic α-helices. They are held in the hydrophobic region of the lipid bilayer by noncovalent forces. Some membrane proteins are transmembrane pores or water-filled channels with β-barrel structures. The latter are arranged with the hydrophobic residues outside, in contact with the hydrophobic component of the bilayer, while the hydrophilic residues point inwards. Peripheral membrane proteins may be associated with a membrane by hydrogen bonding or ionic attractions. They may also be anchored by a fatty acid attached with its hydrocarbon chain inserted into the lipid bilayer.
Page reference: Page 109

Question 4

Which of the following statements about the functions of cell membranes is not correct?

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Correct answer:

1. d) Cell membranes are permeable to most inorganic ions.

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Biological membranes have a lipid bilayer structure, the constituents of which are polar lipids. There are many different types of membranes. They are made up of different polar lipids conferring different properties to the membranes. Different cells have different membrane compositions just as different membranes have different membrane functions. The membrane that surrounds a cell is known as the plasma membrane. It maintains the shape of the cell and its contents preventing non-specific leakage. It is impermeable to most molecules other than small hydrophobic ones. Although inorganic ions are very small, they cannot diffuse through a cell membrane because they are surrounded by a shell of water molecules and removal of these creates an energy barrier.
Page reference: Page 110

Question 5

Which of the following statements about the mechanism of the Na+/K+ pump is correct?

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Correct answer:

1. a) The Na+K+ ATPase uses energy to pump Na+ outside the cell and K+ inside.

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The Na+/K+ pump is also called the Na+/K+ ATPase. It is a protein complex composed of two identical α subunits and two β subunits. When the protein is in one conformation it is open to the interior of the cell. In this conformation it binds Na+ but not K+ ions. When the protein is phosphorylated by ATP (on an aspartyl residue), the Na+/K+ ATPase undergoes a conformational change and opens to the outside. It does not bind Na+ in this form but binds K+. When the phosphoryl group is hydrolysed the conformation changes again to release the bound K+ inside the cell. In this conformation Na+ binds again. Overall 3 Na+ ions are transported out of the cell and 2 K+ are transported in. It is called an ATPase because ATP is hydrolyzed to ADP and Pi as Na+ is pumped out of the cell and K+ in.
Page reference: Page 111

 

 

 

Question 1

Which of the following statements about the structure of skeletal muscle is not correct?

Your answer:

1. a) Myofibres of skeletal muscle cells contain numerous myofibrils that are divided into sarcomeres.

Correct answer:

1. d) The arrangement of thin myosin and thick actin filaments give the sarcomeres of skeletal muscle a striated appearance under the microscope.

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Skeletal muscle cells are elongated multinucleate cells called myofibres. Each myofibre contains numerous parallel myofibrils running lengthwise and each one is surrounded by a membranous sac, the sarcoplasmic reticulum. Myofibrils are divided into regular segments known as sarcomeres. Each sarcomere is made up of a regular arrangement of thick (myosin protein) and thin (mainly actin protein) filaments that give skeletal muscle a striated appearance under the microscope. Contraction occurs when the thick filaments move the thin filaments along them by means of a ratchet mechanism. The thin filaments are pulled towards the centre of the sarcomere. Z discs of proteins at each end of the sarcomeres have the actin filaments attached to them. The cell membrane or sarcolemma has nerve endings (that release the signal that triggers contraction) in close proximity. Skeletal muscle is under voluntary nerve control and contracts rapidly.
Page reference: Page 125

Question 2

Which of the following statements about the structure of the thick and thin filaments in skeletal muscle is correct?

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Correct answer:

1. b) Thin filaments of skeletal muscle have plus and minus ends.

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Thin filaments are mainly polymers of actin. They have directional polarity and the ends are referred to as plus (+) and minus (-). Each thin filament consists of two actin polymers (with the same polarity) coiled around each other and anchored to Z discs at the (+) end. Thick filaments are made of several hundred myosin molecules. Each myosin molecule consists of a dimer structure formed from two heavy polypeptide chains arranged in a coiled-coil configuration to form a rigid rod. Each rod terminates in a myosin globular head that is perpendicular to the actin filaments. Each actin monomer (in a filament) can bind a single myosin head. Each myosin head has two dissimilar light chains attached to it. The myosin molecules are arranged in a bipolar fashion so that the heads point at both ends of the thick filament. A large protein, titin, holds the thick filaments in the correct orientation with respect to the thin filaments.
Page reference: Page 127

Question 3

Which of the following statements about the contraction of skeletal muscle is correct?

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Correct answer:

1. d) The power stroke of skeletal muscle contraction occurs when the myosin head releases ADP and Pi.

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Skeletal muscle cells are made up of a regular arrangement of thick (myosin) and thin (actin) filaments. The latter are anchored to Z discs (proteins) at their plus (+) end. Thick filaments form rigid rods, each terminating in a globular head perpendicular to the thin filaments. During contraction thick filaments move the thin filaments by means of a ratchet mechanism pulling the thin filaments and their attached Z discs towards the centre of the thick filament. A myosin head cannot bind to actin (relaxed state) when ATP is bound to it. When ATP is hydrolysed (myosin head is an ATPase) a conformational change occurs. A force is exerted by the myosin on the actin filament. This is the primed state (the ADP and Pi remain attached to the head). The myosin head can now bind to the actin filament if Ca+2 is present. ADP and Pi are released liberating energy and forcing the thin filament to slide causing a contractile force. This is the power stroke.
Page reference: Page 128

Question 4

Which of the following statements about the role of calcium (Ca2+) during skeletal muscle contraction is correct?

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Correct answer:

1. d) Ca2+ released into a myofibril by the action of a nerve impulse binds to a site on troponin to initiate contraction.

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Skeletal muscle contraction is initiated by a nerve impulse causing Ca2+ ions to be liberated into the myofibril from the surrounding sarcosplasmic reticulum. The nerve impulse to the muscle cell causes the normally closed voltage-gated Ca2+ channels to open and release Ca2+ from into the myofibril. The Ca2+ binds to one of the subunits of the trimeric protein on the actin filament called troponin. The latter is associated with another protein called tropomyosin on the actin. Together these block the myosin-binding sites. A conformational change occurs to remove the troponin and tropomyosin from the myosin-binding sites. This allows the myosin head to attach to the actin filament provided the ATP on the myosin head has been hydrolysed to ADP and Pi. The power stroke that causes the actin to slide (by the force exerted by myosin) occurs when ADP and Pi are released (energy is liberated). Withdrawal of Ca2+ terminates the contraction event.
Page reference: Page 127

Question 5

Which of the following statements about smooth muscle contraction is correct?

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Correct answer:

1. c) Phosphorylation of a myosin light chain allows actin-myosin binding in smooth muscle.

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Smooth muscle cells do not contain myofibrils or sarcomeres. They are smaller than striated muscle cells. They have a single nucleus. In addition contraction is much slower than in striated muscle and actin filaments run the length of the cell and they are anchored to the cell membrane. One of the light chains (the p-light chain) in the myosin heads inhibits myosin from binding to the actin filament, and thus prevents contraction. Nerve impulses cause Ca2+ gates in the plasma membrane to open allowing Ca2+ to enter the cell. Ca2+ activates a myosin light chain kinase, via a protein called calmodulin. The kinase phosphorylates the p-light chain (using ATP) abolishing the inhibitory effect of myosin binding to actin. Contraction occurs. When Ca2+ levels fall, a phosphatase enzyme catalyses the dephosphorylation of the myosin light chain and relaxation occurs.
Page reference: Page 132

 

 

 

Question 1

In which of the following situations would cells die by necrosis, not apoptosis?

Your answer:

1. a) Removal of virus infected cells.

Correct answer:

1. c) Removal of heart muscle cells damaged by oxygen depletion following cardiac infarction.

Feedback:

Virus infected cells, cells with DNA damaged beyond repair, and cells which have become superfluous, such as growing neurones which fail to make synaptic connections with other cells, are all stimulated to destroy themselves by an apoptosis mechanism. Cells which have become accidentally damaged in some traumatic way, including long term oxygen deprivation such as is caused by cardiac infarction, burst and release their contents when they are unable to synthesize enough ATP to maintain their integrity. This produces an inflammatory response characteristic of necrosis.
Page reference: 512

Question 2

Which cellular organelles are involved in the initiation of the intrinsic pathway of apoptosis?

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Correct answer:

1. b) mitochondria

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The initiating procaspases of the intrinsic apoptosis pathway are attached to the outer membrane of the mitochondria. They are released when the intrinsic pathway is initiated, forming a multimolecular cluster called the apoptosome in which the clustered procaspases can self activate. Thus the mitochondria are the organelles involved in the initiation of internally stimulated apoptosis. In some circumstances incorrectly folded proteins which accumulate in the endoplasmic reticulum can be transported to the cytoplasm where they trigger apoptosis directly. However, this is an unusual mode of initiation which occurs rarely.
Page reference: 513

Question 3

Which of the following proteins is not part of the apoptosome which initiates apoptosis by the intrinsic pathway?

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Correct answer:

1. b) Bcl-2

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The apoptosome is a multimolecular complex probably made up of seven molecules each of apaf -1, cytochrome c, and procaspase 9 together with at least seven molecules of ATP. This clustering of procaspase 9 in some way allows it to self activate by proteolytic cleavage to form the active intitiator, caspase 9. In non-apoptotic cells procaspase 9 is bound to the outer membrane of the mitochondrion, attached to apaf-1, which is itself bound to an intrinsic membrane protein, bcl-2. Cytochrome c, released from the mitochondrion in response to apoptotic signals, competes with bcl-2 for binding to the apaf-1 / procaspase 9 complex, which it releases from the mitochondrial membrane allowing it to form the apoptosome.
Page reference: 513

Question 4

Which of the following are killed by the extrinsic apoptosis pathway?

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Correct answer:

1. a) Virus infected cells.

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The extrinsic apoptosis pathway is triggered by signals from outside the cell. Virus infected cells are recognized by cytotoxic T-lymphocytes which activate the extrinsic apoptosis pathway. Other signals which arise outside the cell can activate intrinsic apoptosis. For example nerve cells which fail to make profitable connections do not receive a growth factor signal. The removal of this signal allows intrinsic apoptosis to be activated. Factors which stress and damage cells, such as toxins, radiation or short term oxygen depletion, can stimulate intrinsic apoptosis even though they originate outside the cell. This may be because they damage DNA, though other more specific trigger mechanisms may be involved. Damaged DNA in a cell results in an increased amount of the protein P53. This initially increases production of DNA repair enzymes, but if the DNA is not repaired in a reasonable time P53 signals the activation of the intrinsic apoptosis pathway.
Page reference: 514

Question 5

Which of the following proteins is a death receptor which triggers the extrinsic pathway of apoptosis?

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Correct answer:

1. d) fas

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The fas protein is a member of the tumour necrosis factor receptor superfamily. Cytotoxic cells, which are able to signal target cells to undergo apoptosis, carry on their surface a protein complementary to fas, called the fas ligand. When this binds to fas on a target cell it stimulates the initiation of apoptosis. First an adaptor protein, the fas activated death domain (FADD) binds to fas. Procaspase 8 then binds to FADD. Because fas is trimeric, three FADD / procaspase 8 complexes bind to it, producing a close cluster of procaspase 8 molecules, which are able to self activate. Thus fas is the death receptor, which stimulates apoptosis using the downstream proteins FADD and procaspase 8. Fas ligand is an apoptosis trigger carried by the cytotoxic cell, which can initiate apoptosis in any cell carrying fas (most cells carry fas on their surfaces). The cytotoxic cell binds to its target cell using specific receptors such as the T-cell receptor.
Page reference: 514

 

 

Question 1

In order to enter the cell cycle a cell must be stimulated from outside. What type of molecule provides this stimulation?

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Correct answer:

1. c) Cytokine growth factors

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The cell is stimulated to enter the cell cycle from outside by cytokine growth factors, which are peptides secreted by nearby cells. In some cells, particularly in the immune system, the growth factor may be a membrane protein of the stimulating cell. These growth factors activate the cell by binding to receptors in the plasma membrane which have growth factor binding domains on the outer face of the membrane. Binding of a growth factor stimulates the cell by activating a tyrosine kinase enzyme which is either an internal domain of the receptor or is picked up from the cytoplasm by the activated receptor. Message transduction mechanisms stimulated via the tyrosine kinase initiate the cell cycle by stimulating synthesis of cyclins, which are able to activate constitutively inactive cyclin dependant kinases.
Page reference: 508

Question 2

In which phase of the cell cycle is DNA replicated?

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Correct answer:

1. b) S phase

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DNA replication takes place only in the S (synthesis) phase of the cell cycle, which is part of interphase. In the other parts of interphase, the gap phases G1 and G2, which precede and follow S phase respectively, parts of the DNA are transcribed, protein synthesis takes place and the cell grows, but DNA is not synthesized. In the relatively short M (mitosis) phase the two copies of the replicated chromosomes are separated and the cell divides. In this phase the chromosomes are highly condensed, with the DNA tightly wrapped around histones. In this state they are inactive and neither DNA replication or transcription takes place.
Page reference: 507

Question 3

The passage of a cell through the stages of the cell cycle is controlled by protein kinases which phosphorylate many different proteins at appropriate times. What are these protein kinases called?

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Correct answer:

1. a) Cyclin dependant kinases

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Cyclin dependant kinases are the key enzymes which carry out the phosphorylations which regulate progression through the cell cycle. The activity of Cyclin dependant kinases is closely regulated and varies continuously throughout the cycle, but the actual amounts of Cdks present does not vary very much. Instead, their activity is controlled by cyclins and by phosphorylation. Binding of cyclins and phosphorylation by activating kinases activates Cdks. They may also be inhibited by binding proteins and by phosphorylations including that carried out by protein kinase Wee 1.
Page reference: 508

Question 4

Which of the following is not a characteristic of the cyclins involved in the cell cycle?

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Correct answer:

1. c) Cyclins are the sole controllers of cyclin dependant kinase activity.

Feedback:

The most important controllers of the cell cycle are the cyclins, not the cyclin dependant kinases which actually carry out the phosphorylations which control the cycle. Whilst cyclin dependant kinase levels do not change much throughout the cycle, they are not active unless they are bound to cyclins, and cyclin concentration changes rapidly throughout the cycle. In general cyclins are synthesized at the start of the cycle phase they activate and destroyed by proteolysis at its end. Cyclins also influence the substrate proteins phosphorylated by Cdks. The same Cdk phosphorylates a different set of proteins when activated by different cyclins. However, cyclins are not the only regulator of Cdk activity. Though activation of Cdks requires cyclin binding, the cyclin - Cdk complex can be further activated, or inhibited by phosphorylation by specific kinases.
Page reference: 508-9

Question 5

At which cell cycle checkpoint is the cell cycle halted if the cell's DNA is damaged?

Your answer:

1. d) G0 - G1

Correct answer:

1. a) G1 - S

Feedback:

The G1 phase is the most variable in length in the cell cycle, and usually the longest. The G1 - S checkpoint is called the restriction point. Once the cell has passed this point it is committed to go through to mitosis, and can only avoid this by undergoing apoptosis, which will be triggered if the cell cannot meet any of the requirements for passing later checkpoints in the cell cycle. If the cell's DNA is damaged this will normally be detected by proteins which recognize and bind to sections of single stranded DNA which is characteristic of strand breaks, or stalled replication forks. These trigger a mechanism which holds the cell at the restriction point, giving time for repair enzymes to repair the damaged DNA. If the damage is not repaired within a reasonable time the same mechanism will force the cell into apoptosis.
Page reference: 509-10