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7/29/2019 Lecture Covering Details of the Cell Cycle
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Cell Cycle and regulation
Maulik P. Suthar
Cell Biotechnology
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70kg human ~ 1013
cells
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Two processes must alternate during eukaryotic
cell division
Genome must be replicated in S phase
Genome must be halved during M phase
Cell cycle events must behighly regulated in a temporal manner
Genetic and molecular studies in diverse
biological systems have resulted in identification
and characterization of the cell c cle machiner
The Cell Cycle
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G1
Cell CycleG0
6-8 h
DNA, RNA,
Protein
3-4 h
RNA, Protein
1 h
Mitosis, Cytokinesis
S
G2 Cyc DsCDK4,6
Cyc B/ACDK1
Cyc ACDK2
M
Cyc ECDK2
6-12 h RNA, Protein
p53pRb
LaminH1
Abl
The cell cycle engines
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The cell cycle engines
Cyclin Dependent Kinases (CDKs)
CDK
cyclin
substrate
ATP
P
product + ADP
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Cyclin D-CDK4
Cyclin E-CDK2
Cyclin A-CDK2
Cyclin B-CDC2
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Variation in Cell Cycle Cyclins
M G1 G2S M G1
Start
Cell cycle phases
Cyclin-dependent kinases
D E A B(A)cyclins
Cdk4 Cdk2 Cdk1
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CDK activity
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Cyclin D-CDK4
Cyclin E-CDK2
Cyclin A-CDK2
Cyclin B-CDC2
CDKinhibitors
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Cell Cycle Characteristics
Temporally ordered events
Irreversibility
Oscillations
Checkpoints
Positive and negative feedback loops
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pRbpRb
Cell Cycle Regulation
CDK2CE
E2FEnzymes forDNA synthesis
Passage fromG1 to S
DNA damage1. CDK phosphorylation
2. C degradation
3. C & CDK synthesis
4. CDK inhibition
pRb
P
Active p53
p21
pRb
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Positive Feedback Loop
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CDK
cyclin
substrate
ATP
P
product + ADP
p27kip1
CDK
cyclin Inhibited
p27kip1
Model of p27kip1 Function
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Inhibited
p27kip1
CDK
cyclin
Switch
Active
CDK
cyclin p27kip1
P
p27kip1
P
Cell cycle
progression
Switching between Inhibitor and substrate functions
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Review Questions
What are and what happens during the phases of thecell cycle?
Which proteins are involved in the regulation of thecell cycle?
Which cyclins and cyclin-dependent kinases are mostimportant in individual phases of the cell cycle?
What are four mechanisms for regulating cyclin-dependent kinase activity?
What role do p53, p21, and pRb play in the G1 to S
transition?
Questions
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What causes cyclin degradation to turn on and offperiodically?
Why dont rates of synthesis and degradation balance
each other?
There must be some mechanism for switching
irreversibly between phases of net cyclin synthesis and
net cyclin degradation.
Questions
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The Cell CycleThe Cell Cycle
Cells must divide to maintain maximumCells must divide to maintain maximum
efficiency.efficiency.
Mitosis is the process in which somaticMitosis is the process in which somatic
(body) cells divide to form a new cell.(body) cells divide to form a new cell.
Mitosis consists of four phases.Mitosis consists of four phases.
Interphase is the period in between eachInterphase is the period in between eachmitotic cell division.mitotic cell division.
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Interphase
Interphase is made of 3 stages.
The Gap 1 and 2 or G1 and G2 phase is
when cells grow and make RNA, proteins,
and other macromolecules. The S or Synthesis phase is when the cell is
making DNA.
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DNA Replication
During the S phase of the cell cycle, DNA
replicates.
A short section of the DNA uncoils.
New nucleotides bond to the open
sections of the DNA.
The new and old sections of DNAseparate and now there are 2 DNA
strands.
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Interphase
ATP is synthesized.
Damaged parts are repaired.
Wastes are excreted. Proteins are made.
Organelles are formed.
Chromosomes are copied.
Specialized tasks are performed .
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Prophase
Longest phase.
Chromatin coils.
Nucleus disappears.
Centrioles migrate.
Spindle forms.
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Metaphase
Chromatids attach to spindle fibers. Chromatids migrate to equator of spindle.
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Anaphase
Centromere splits.
Chromatids are separated.
Chromatids are now called chromosomes.
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Telophase
Cytoplasm divides. Nucleus reappears.
Chromosomes uncoil.
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Cytokinesis
In the process
called cytokinesis,
the cytoplasm
divides and twoidentical daughter
cells are formed.
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