1. --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 Previously:

2. How and where does the cell check its cycle?

3. 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

4. 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

5. Mitotic checkpoint and chromosome # Why/How could this be more effective than using an accumulation of positive signals? Sometimes going forward requires silencing the negative

6. 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.

7. CAK (Cdk activating kinase) and CKI (cyclin kinase inhibitors) act on formed complexes to regulate function Regulating the complex

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

10. How do you make or get rid of the complex– (cycling the cyclins to ‘off’) Transcriptional control Degradation control Ubiquitination Proteasome

11. Some checkpoints require ‘all clear’ message Figure 17-33 DNA damage and p53 stability

12. Overview of Cell Cycle regulation ‘complete’ Next: Looking at the different hypotheses for the molecular reasons for aging