Cell cycle phases Cyclins CDKs
action of cyclins and cyclin-dependent kinases
(CDKs) of which there are several. The activity of
the CDKs is dependent on interaction with
cyclins. However, the presence of CDK
inhibitory proteins, CIPs, results in inhibition of
the activity of CDKs. CIPs bind and inhibit
CDK1, 2, 4, and 6 complexes. Thus, an increase
in the activity of p53, which occurs in response to
DNAdamage, results in a block to cell-cycle progreCell cycle phases
- Checkpoints control transitions between phases of cell cycle.
- This process is regulated by cyclins, cyclin-dependent kinases (CDKs), and tumor suppressors.
- Mitosis (shortest phase of cell cycle) includes prophase, metaphase, anaphase, and telophase.
- G1 and G0 are of variable duration.
- Regulation of cell cycle
- Constitutive and inactive.
- Regulatory proteins that control cell cycle events
- phase specific
- activate CDKs
- Cyclin-CDK complexes –
- Must be both activated and inactivated for cell cycle to progress.
- G1/S cyclin: They activate Cdks in late G1 and their level fall in S phase.
- S cyclin: They stimulate DNA replication and their level remains high until mitosis.
- M cyclin: Activate Cdks that stimulate entry into mitosis at the G2/M checkpoint.
- G1 cyclins: Governs the activities of G1/S cyclins.
Don’t Enter After the Bell – How to
- Cyclin D/E – G1 ➡ S
- Cyclin A – S ➡ G2
- Cyclin B – G2 ➡ M
- Tumor suppressors
- p53 and hypophosphorylated Rb normally inhibit G1-to-S progression
- mutations in thes genes result in unrestrained cell division (e.g., Li-Fraumeni syndrome).
- CELL TYPES
- Remain in G0, regenerate from stem cells.
- Neurons, skeletal and cardiac muscle, RBCs.
- Stable (quiescent)
- Enter G1 from G0 when stimulated.
- Hepatocytes, lymphocytes.
- Never go to G0
- divide rapidly with a short G1.
- Most affected by chemotherapy.
- Bone marrow, gut epithelium, skin, hair follicles, germ cells.
- A patient has been diagnosed with a melanoma, and molecular analysis has indicated that the tumor has sustained a loss of p16(INK4) activity (inhibitor of cyclin-dependent kinase 4). Such a gene would be best classified as which of the following?
(A) A dominant oncogene
(B) A tumor suppressor
(C) A proapoptotic factor
(D) An antiapoptotic factor
(E) A growth factor
13 The answer is B:
A tumor suppressor. Cyclin-dependent kinase inhibitors (CKI) act to block the action of kinases that are activated by cyclins .When such an activity is lost (meaning that the gene products from both chromosomes are inactive), uncontrolled cell proliferation can result. Since the activity must be lost, such genes are classifi ed as tumor suppressors, as opposed to the dominant oncogenes, in which an activity is gained via mutation or inappropriate gene regulation. The CKIs are not involved in apoptosis, nor do they act as growth factors.
- In which phase of the cell cycle DNA is synthesized:
- M Phase
- Gt Phase
- S Phase
- G2 Phase
ANS: C. DNA is synthesized during the S-phase of the cell cycle, this period known as synthetic phase. Mammalian cells contain large quantity of DNA polymerase enzymes. M phase (mitosis) is the cell division stage. Gl phase (gap-1) and G2 phase (gap-2) occurring before and after S phase.
- Gl phase RNA and protein contents increase.
- Cytoplasmic enalargment is seen in G2 phase.
3 Which one of the following statement is correct regarding cy clins?
- They are inhibitors in replication
- They control cell cycle
- They are circular single stranded DNA
- They are not able to phosphorylate specific proteins
ANS: B. Cyclins are proteins and their concentrarion increase or decrease through out the cell cycle, that’s why they are named as cyclins. These cyclins activate different cyclin dependent kinases (CDK1, 2, 4, 5 and 6) which phosphorylates specific substrate for the transition of one phase of cell cycle to another.
- Which of the following cellcycle proteins is involved in DNA damage mediated cell-cycle arrest?
- cyclin A
- cyclin D
The p53 protein is a tumor suppressor whose
function is to ensure that cells with damaged
DNAdo not progress through the cell cycle until
that damage is repaired. The major response to
p53 action is an increase in the expression of the
p21CIP gene. Progression through the cell cycle
requires, among other activities, the concerted
6 .ALL of the following are example of stable cell exept
C – smooh muscle
D – GI epethelia
GI epethelia are labile cell