--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

Previously:

How and where does the cell check its cycle?

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

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

Mitotic checkpoint and chromosome #

Why/How could this be more effective thanusing an accumulation of positive signals?

Sometimes going forward requires silencing the negative

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.

CAK (Cdk activating kinase) and CKI (cyclin kinase inhibitors) act on formed

complexes to regulate function

Regulating the complex

Great it’s active—what does it do? (the cyclin-Cdk complex)

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

Transcriptional control

Degradation controlUbiquitinationProteasome

Some checkpoints require ‘all clear’ message

Figure 17-33DNA damage and p53 stability

Overview of Cell Cycle regulation ‘complete’

Next: Looking at the different hypotheses forthe molecular reasons for aging