Chapter 9 Flashcards
(41 cards)
What are the 4 phases of the cell cycle?
G1, S, G2 and M
What happens in the S phase?
Replication of genome
What happens in the M phase?
Segregate the replicated genome into two daughter cells
What is G0?
A quiescent state in which a cell cease proliferation because of insufficient nutrients, lack GF or upon differentiation.
What is a replication fork?
When DNA polymerase is attached to ssDNA, and replicate the DNA so leaving 2 dsDNA in its wake.
How does a cell ensure that each stretch of DNA is replicated only once?
By allowing each DNA replication origin site to “fire” once pr. cell cycle. Each initiation site will be bound by a pre-prereplication complex which assemble after mitosis, and when it is bout the origin site is licensed for replication.
Define cytokinesis
The process where a mother cell splits into two daughter cells.
What are the phases of mitosis?
Prophase, prometaphase, metaphase, anaphase, telophase (some include an interphase before prophase)
Which factors are deciding if a cell is allowed to enter S-phase?
A combination of extra and intracellular signals, in addition to proximity to neighboring cells. The external ligands are usually referred to as growth factors
What is the restriction point and where in the cell cycle does it occur?
It determines the cellular response to DNA damage or other mistakes/deficiencies PRIOR TO REPLICATION- ie. it is there to repair mutations that has occurred independently of mistakes that can occur during replication (from UV light, carcinogens, radiation etc)
What happens to the restriction point in cancer cells?
The control over the restriction point is loosened, as the cells proliferate without the appropriate combination of extracellular signals.
Name two molecular mechanisms which are particularly central to cell-cycle regulation
Cyclin-dependent kinases and E3 ubiquitin ligases
How are CDKs activated?
By binding to CYCLIN, which leads to phosphorylation of the CDK and their activation. CYCLIN also influences substrate selection by the CDK and specify the intracellular location of CDK activity
Which cell function is dependent on ubiquitin mediated proteolysis?
Destruction of important cell cycle proteins
Name the different cyclin and CDK combinations which have been best documented?
CDK 1 + A/B
CDK 2 + A/E
CDK 4/6 + D
CDK 7 + H (works as an activator for other CDKs)
Name 2 important inhibitory control mechanisms of CDKs
MYT1 and WEE1, and CDK inhibitors such as INK4/CIP/KIP
How does the intracellular level of cyclins vary through the cell cycle?
No variation of cyclin D throughout the cell cycle, high levels of A and B through S and G2, very low through M and G1.
When is the cells restriction point in the cell cycle?
In G1- will need to pass through the restriction point to enter S-phase
What may be the causes for a cell to arrest in G1?
DNA damage, lack nutrients, excessive contact neighbour cells, too small in size, lack of extracellular growth factor stimulus
Where in the cell cycle are the checkpoints?
G1, S and G2/M
How is cell arrest induced in G1 due to genome damage?
DNA damage autophosphorylate ATM/ATR, together with DNA-PKs they activate multiple proteins which form a platform on which repair proteins can assemble. They also stabllize P53, which works as a transcription factor for p21 which is and CDK D/E, cyclin 1 inhibitor resulting in cell cycle arrest.
What are the 2 cell states and which CKDs are high when?
Anaphase to S1 - low CKD 1 and 2, high APC/C
What is the molecular basis of the restriction point in G1?
Growth factors stimulate cyclin D-CDK 4/6 which phosphorylates the 3 proteins Rb, p130 and p 107- they are released from the transcription factor E2F = allow E2F to promote transcription of Cyclin E and Cyclin A. This overturns the G1 state resulting in elevated CDK 1+2 activity and the cell enter S-phase.
Which known oncogene is involved in cell growth?
c-MYC
