Cell Cycle Control

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Cell Cycle Control Lodish Chapter 21

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Cell in metaphase
DNA
Spindle pole
Mitotic spindle
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The budding yeast S. cerevisiae
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Multiple cyclins direct kinase activity of Cdc28
during different cell-cycle phases
Cdc28-Clb1/2
Cdc28-Clb3/4
Once a cell passes START, it is committed to
undergo division
Cdc28-Cln3
Cdc28-Cln1/2
Cdc28-Clb5/6
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CDKs are highly conserved throughout evolution
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Multiple cdks and cyclins regulate passage of
mammalian cells through the cell cycle
Cdc2/Cdk1-cyclin B Cdc2/Cdk1-cyclin A
Cdk4-cyclin D Cdk6-cyclin D
Restriction point is analogous to START
Cdk2-cyclin A
Cdk2-cyclin E
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phosphorylation by Cdc25 kinase
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Degradation of the S phase inhibitor p16 promotes
passage through the restriction point by
inhibiting Retinoblastoma (Rb)
p16
p16
Retinoblastoma is a tumor suppressor

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Cdc28-Clb ensures that replication at each origin
is initiated only once during the cell cycle
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Checkpoints in cell cycle regulation
mitosis
securin
Prophase
Anaphase
G1 phase
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The mechanism of p53-induced cell-cycle arrest in
response to DNA damage
if DNA damage cannot be repaired
Direct inhibition of PCNA (replication clamp)
p53 is a tumor suppressor
APOPTOSIS
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G1 and G2 arrest in cells with damaged DNA
depends on the p53 tumor suppressor
p53 mutations drive cells into S phase, they are
found in gt 50 of all cancers.
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What you need to know Cell cycle is regulated by
cyclin-dependent kinases Passage through
START/restriction point is coupled to decision
to undergo cell division. Therefore, once cell
initiates DNA replication, it is committed to
divide (block replication initiation should
prevent proliferation). Rb inactivation triggers
S phase in humans S phase Cdk activity has dual
role 1) activates replication in beginning of S
phase and 2) prevents reformation of pre-RC once
an origin has fired. You need re-replication
control because you want exactly one and only one
copy of your DNA. p53 (active as a tetrameric
transcription factor) is an important
checkpoint signaling protein, induces p21, a CDK-
and PCNA inhibitor, which leads to cell cycle
arrest, such that DNA can be repaired before the
cell cycle progresses.