Week 5- cell division- Holy Flashcards
define G0
G0-cells leave the cell cycle- no more cells are needed
time spent in
1) S phase
2) M phase
1) 8-12 hrs
2) 1 hr
G1
gap 1- decision whether or not to divide
if cell decides to divide it passes “start” point and now it is committed to starting DNA synthesis and entering mitosis
S phase
where DNA synthesis occurs (xsomes and centrosomes replicate)
- after xsome rep is complete, daughter xsomes (called chromatids) remain connected to each other at the centromere
- specific DNA-binding centromeric proteins are attached to and identify this region
G2
after DNA syn, cells do not immediately divide (G2)
xsomes condense to prepare for mitosis
proteins responsible for driving the cell cycle
CDK’s and cyclins
cohesions
Cohesions- multi-protein complexes that help keep replicated xsome pairs (daughter chromatids) together, by encircling them, until the time when it is appropriate to separate them
condensins
multi-protein complexes that are involved in xomse condensations (condense so they can be more easily separated)
most important feature of mitosis
each daughter cell receives a complete set of all the xsomes originally present in the mother cell ==> identical daughter cells
what proteins are responsible for driving the cell cycle
how do they do this
CDK’s and cyclins
cyclins bind to CDK’s to form a complex that can further phosphorylate regulatory and transcription factors to help move the cell cycle along.
how are CDK’s and cyclins regulated
regulated by being phosphorylated/dephosphorylated
Wee1 kinase
adds a phosphate that inactivates Cdk’s, and Cdc25 phosphatase removes the phosphate to activate it
Cki’s (p27)
proteins that bind to the cyclin-Cdk complex to inactivate it
3 ways to regulate CDK activity
1) presence of cyclin
2) specific patterns of CDK phosphorylation
3) presence of Cki’s
How are positive feedback loops used in cell cycle regulation?
Positive feedback works to activate more Cdc25 to activate more Cdk’s, and inhibits Wee1 to inhibit its deactivating activity
cyclin/CDK pairs that drive:
G1
M
G1: Cyclin D, CDK4 or 6
M: Cyclin B, CDK1
best pathway for cell cycle regulation
growth factor signaling
regulation of G1/GO phase (MAP kinase pathway)
growth factors(mitrogen) dimerize and activate Ras ⇒ activates MAP kinase cascade ⇒ a P’d Map Kinase can enter the nuclease ⇒ activate transcription factors via phosphorylation ⇒ transcribe early response genes (Myc)⇒ Myc activates transcription of late response genes (cyclin D) ⇒ Cyclin D binds to CDK and becomes active ⇒ active Cdk complex phosphorylates Rb gene (which normally inhibits a transcription factor- E2F)⇒ phosphorylated Rb gene in now inactive which menas E2F can be active ⇒ E2F activates transcription of S phase cyclins to proceed with S phase
Rb
when phosphorylated it is inactive and can’t in turn inactivate E2F
E2F transcription factor
activates transcription of of S phase cyclins when Rb is inactive (P’d)
activate genes that make proteins needed to DNA rep
purpose of Myc genes
to activate genes that encode for cyclin D which can bind to CDK
ORC’s
ORC’s- origins of replication- where replication can begin (multiple of these on xsomes)
what triggers S phase
triggered by production of S phase cyclins from the cyclin-D complex from G1
pre-RC
early in G1, a complex of initiator proteins assembles on replication origins for form pre-replication complex
when can pre-RC bind to replication origins
can only bind when unphosohorylated
-since they are substrates of CDK, they can only bind in G1, when the overall CDK activity is low (or else they would get P’d)
what divides the cytoplasm during cytokinesis
a contractile ring made up of actin and myosin
steps for entering M phase
M-Cyclin (Cyclin B) increases ⇒ cyclin B associates with CDK1 forming M-CDK ⇒ M-CDK is phosphorylated by an inhibitory kinase (Wee1) and an activating kinase (CAK) ⇒ inhibitory P’s keep M-CDK activity low ⇒ when Cdc25 gets activated (by phosphorylation) it removes the inhibitory P’s form M-CDK
where are the cell cycle check points
1) entering S phase
2) entering M phase
3) leaving M phase
how is p53 used in cell cycle check points
DNA damage → activation of ATM/ATR which then activates Chk1/Chk2 kinase → Chk1/Chk2 phosphorylate p53 and activate it (causing release of Mdm2) → p53 binds to DNA to promote p21 gene → p21 gene makes CKI’s that inhibit cyclin/Cdk to halt cell cycle