lec 40 Flashcards
Commitment to cell reproduction (G1 checkpoint)
If answer is no –> G0
If answer is yes —> makes G1-Cycline which attaches to G1-Cdk
Synthesis of DNA replication proteins
G1-Cdk indirectly activates TFs
G1-Cdk makes phosphorous which acts on the target
G1-Cdk inactivate
Rb proteins on the TFs which allow it to go to work
RB is the physical target of G1-Cdk
DNA replication begins at the
ORI travels left and right
we have one per 40k bp
What proteins are sitting on the ORIs
ORCs and helicases
G1 Cdk second target
S-Cdk
S-Cdk targets
ORCs (phosphorylates them)
Causes them to fire, creating a replication fork and beginning replication
The ori’s cannot fire
A second time
ORCs can only be phosphorylated once
Not enough Helicases available
Centrosome replication (S phase)
Need two centrosomes per cell for mitosis
S-Cdk also indirectly activates
Centrosome replication with phosphorylation
Purpose of mitosis
To replicate the nucleus
How does the cell tell if DNA replication is done
If there is any single stranded DNA left, the cell can recognize it
DNA repair could also be a sign
M-Cdk is activated when
DNA replication and repair are complete
Failure to pause cell cycle
Chromosomes break during anaphase
M-Cdk first target
MTs
M-Cdk activates MT regulatory proteins and make the MTs very active and centrosomes move apart
M-Cdk target 2
Nuclear lamina
Phosphorylates and is dismantled
M-Cdk target 3
M-Cdk inactivates and separates nuclear pores
Phosphorylation of lamina and pores causes
Membrane to separate from chromosomes so that chromosomes can attach
M-Cdk target 4
Condensin proteins
Activates condensin
5th target of M-cdk
Myosins are temporarily inactivated
Sister chromatid separation (metaphase checkpoint)
Preparation
Cohesion proteins= sister chromatids attachment
Kinetochore proteins= microtubule attachment
Trigger for sister chromatid separation
APC which is activated by M-Cdk
Inhibited by unattached chromosome (which is after metaphase)
APC target
Cohesions
Destroys them indirectly
APC destroys
Securin which is attached to separase
Separase
Destroys cohesions
Exit from mitosis preparation
Complete set of chromosomes at each pole of cell
Trigger for exiting mitosis
APC destroys M-Cdk (final target for APC)
Once M-Cdk is removed
All phosphates from M-Cdk are also removed and all targets are inactivated
Reestablishment of nucleus
Each chromosome gets a coating of Nuclear Lamins and ER membrane as it expands
Each chromosome gets its own coating of nuclear envelope
Nuclear envelope coating must be
Tight to exclude cytosolic proteins
once each Chromosome has a coating
They fuse into a single nucleus
Why are nuclear pores important
To allow the nuclear proteins to reimport back into the nucleus but avoid cytosolic proteins by using an NLS signal that only the nuclear proteins use
Cytokinesis
Done by actin and myosins
M-Cdk places a phosphate on the myosin which inactivates it
Once M-Cdk is broken down after mitosis, the inactivating phosphate is removed and myosin can then perform cytokinesis
