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Previously:. --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 Balances Balancing cell proliferation and cell death.

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previously
Previously:

--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 Balances

Balancing cell proliferation and cell death

slide3
Basic controls needed

clock/timer mechanism

ensure correct order of events

work like binary switches

adaptability

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

slide4
What needs to be checked for?

Externally?

presence of nutrients

presence of space

presence of cell growth signals

absence of inhibitory signals

Internally?

removing negative blocks

activation of steps by

particular complexes

checking for damage before continuing

sometimes going forward requires silencing the negative
Sometimes going forward requires silencing the negative

Mitotic checkpoint and chromosome #

Why/How could this be more effective than

using an accumulation of positive signals?

sometimes checkpoints require particular combinations
Sometimes checkpoints require particular combinations

Figure 17-16

Figure 17-17

Complex can only be active when together.

Complex only together when cyclins present.

And cyclins……cycle.

regulating the complex
Regulating the complex

CAK (Cdk activating kinase) and

CKI (cyclin kinase inhibitors) act on formed

complexes to regulate function

how do you make or get rid of the complex cycling the cyclins to off
How do you make or get rid of the complex– (cycling the cyclins to ‘off’)

Transcriptional control

Degradation control

Ubiquitination

Proteasome

some checkpoints require all clear message
Some checkpoints require ‘all clear’ message

DNA damage and p53 stability

Figure 17-33

slide12
Overview of Cell Cycle regulation ‘complete’

Next: Looking at the different hypotheses for

the molecular reasons for aging

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