Lecture 28 - Cell Cycle I Flashcards
What are the major chromosomal events in the cell cycle?
L28 S15
- chromosomal duplication
- chromosome segregation
- cytokinesis
What are the four phases of the cell cycle?
L28 S17
Interphase:
- G1 phase
- S phase
- G2 phase
M phase
What are the different checkpoints in the cell cycle and what is checked for at each checkpoint?
L28 S20
Checkpoint I (start):
- is environment favorable to replication
- commits cell to chromosome duplication
Checkpoint II (G2/M):
- checks that all DNA is replicated
- checks that environment is favorable for division
Checkpoint III (metaphase-to-anaphase):
- checks that all chromosomes are attached to mitotic spindle
- triggers chromatid separation and cytokinesis
What group of molecules are responsible for control of the cell cycle and how do they do so?
L28 S26
Cdks (cyclin dependent kinases):
- kinases that are activated in the presence of cyclin and phosphorylate downstream proteins related to cell cycle events
- levels are constant throughout cycle but activity varies
Cyclins:
- proteins whose levels rise and fall (cycle) during cell cycle
- they activated Cdk activity
What are the classes of cyclin and what are they associated with?
L28 S31-32;34
Slide 34 is very good for this
G1/S-cyclins:
- start cell cycle by allowing progression through START checkpoint
- activates Cdks in late G1
- levels drop in S phase
S-cyclins:
- stimulate chromosome duplication
- bind Cdks after passing though START checkpoint
- levels remain high until mitosis
M-cyclins:
- promotes mitosis by allowing progression through G2/M checkpoint
- levels drop mid mitosis
G1-cyclins:
-don’t care
What are the different classes of Cdks:
L28 S33-34
G1/S-Cdk
S-Cdk
M-Cdk
G1-Cdk:
-don’t care
Describe Cdk in its different levels of inactivity/activity. State what proteins are responsible for changing Cdks level of activity and how.
L28 S35
- in inactive form, the active site of Cdk is blocked by a region of its own called the T-loop
- binding of cyclin moves the T-loop out of the active site, partially activating the Cdk
- phosphorylation of T-loop by CAK (CDK activating enzyme) fully activates the Cdk
What proteins other than cyclin regulate Cdk activity and how do they do so?
L28 S37-38
Wee1 kinase:
-inhibits Cdk activity by phosphorylating “roof” site
Cdc25:
-dephosphorylates “roof” site increasing Cdk activity
CKI (Cdk inhibitory protein):
- binds both cyclin and Cdk in cyclin-Cdk complex inhibiting activity
- controls G1/S-Cdks and S-Cdks in early cell cycle
What is familiar hereditary melanoma and what causes it?
L28 S39-40
- genetic form of melanoma (skin cancer)
- caused by loss of inhibitory activity of the INK4A gene which is a CKI
- results in loss of control of the cell cycle
What is p53 and p21? How do they relate to the cell cycle and how can they cause disease?
L28 S41
- p53 influence the expression of many genes including p21 which it up regulates
- p21 is a CKI
- loss of function of p53 results in low levels of p21 and loss of control of cell cycle
How does proteolysis regulate Cdk activity?
L28 S43-44
- SCF-ubiquitin ligase marks CKIs for degradation
- this occurs in G1 and results in activation of S-Cdks
What role does APC/C play in cell cycle regulation?
L28 S48
Anaphase-promoting complex/cyclosome
Separation of sister chromatids:
- ubiquitinates securin targeting it for proteolysis
- securin binds cohesin as an inhibitor of separase
- separase cleaves cohesin which holds sister chromatids together
Destruction of cyclins:
-ubiquitinates S-cyclins and M-cyclins targeting them for proteolysis
What are PRE-RCs and what role do they play in regulating the cell cycle?
L28 S63-65
Pre-replicative complexes
- bind origins of replication in G1 phase
- replication forks are created in S phase
- no new PRE-RCs are made during mitosis so no new replication forks can be made (DNA can only be replicated once)
- inactivated by S-Cdk and M-Cdk
