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--Background on Werner’s syndrome --Hayflick
His persistence and his ‘limit’ -- Theories of cellular aging -- Introduction to the cell cycle
Now: -- More Cell Cycle
How is it controlled? Checks and BalancesBalancing cell proliferation and cell death
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How and where does the cell check its cycle?
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Basic controls neededclock/timer mechanismensure correct order of eventswork like binary switchesadaptability
Why are these characteristics important?
Khodjakov & Rieder and ‘checkpoints’–They aren’t something that is ‘activated’. The security system is always on — ‘normal’ range of activity and even quick fixes that reset are allowed
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What needs to be checked for?Externally?
presence of nutrientspresence of spacepresence of cell growth signalsabsence of inhibitory signals
Internally?removing negative blocksactivation of steps by
particular complexeschecking for damage before continuing
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Mitotic checkpoint and chromosome #
Why/How could this be more effective thanusing an accumulation of positive signals?
Sometimes going forward requires silencing the negative
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Sometimes checkpoints require particular combinations
Figure 17-16Figure 17-17
Complex can only be active when together.Complex only together when cyclins present. And cyclins……cycle.
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CAK (Cdk activating kinase) and CKI (cyclin kinase inhibitors) act on formed
complexes to regulate function
Regulating the complex
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Great it’s active—what does it do? (the cyclin-Cdk complex)
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How do you make or get rid of the complex– (cycling the cyclins to ‘off’)
Transcriptional control
Degradation controlUbiquitinationProteasome
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Some checkpoints require ‘all clear’ message
Figure 17-33DNA damage and p53 stability
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Overview of Cell Cycle regulation ‘complete’
Next: Looking at the different hypotheses forthe molecular reasons for aging