Unit 11

Question 1

Cell-cycle control system

Answer 1

• Based on cyclically activateed protein kinases
• Phosphorylate & activate multiple proteins involved in DNA replication, mitosis & cytokinesis
• Activate only at appropriate times in cycle, where they quickly become inactive again
• Can be rapidly reversed by reactions carried out by another set of enzymes, protein phophatases

Question 2

Cyclins

Answer 2

• Proteins that bind to cell-cycle kinases before kinases become enzymatically active
• Known as cyclin-dependent protein kinases (Cdks)
• Concentrations vary in a cyclical fashion during cell cycle
  1.) Cyclin B synthesis begins in S phase
  2.) Cyclin B then accumulates & forms complexes w/ M phase Cdk throughout S & G2 phases. Although it associates w/ cyclin B, the M phase Cdk is still enzymatically active
  3.) As cyclin B-Cdk complex forms, M-phase Cdk phosphorylated by
  i.) Activating kinase at site required for its activity
  ii.) Inhibitory kinase, over-rides the activating kinase & inhibits activity
  iii.) Still inactive here
  4.) At the end of interphase, M phase Cdk is activated by specific protein phophatase Cdc25 that removes inhibitory phosphate group, leaving activating phophates
  5.) Once activated, M phase Cdk phophorylates & activates a variety of target proteins required for mitosis in M phase. One target is Cdc25, whose phophorylation further activates phophatase activity (positive feedback loop)
  6.) Towards end of G1 phase, inactivatede M phase Cdk inactivated by proteolic degradation of cyclin B. Inactivation of M phase Cdk leads to exit mitosis, undergo cytokinesis & return to interphase
  7.) Towards end of G1 phase inactivated M phase Cdk dephophorylated by specific protein phosphatase. Inactive, unphosphorylated M phase Cdk kinase now ready to form complex with cyclin B