The Role of Cdc2 Feedback Loop Control in the DNA Damage Checkpoint in Mammalian Cells

摘要: DNA damage inactivates cyclin-dependent kinases (CDKs) and arrests the cell cycle. Following damage, G1-S CDKs are inhibited by a mechanism involving p53-dependent induction of p21Cip1/Waf1; but how Cdc2 is less apparent. We found that signal generated checkpoint in G2 was dominant over from spindle microtubule-assembly checkpoint, because high activity present nocodazole or Taxol-arrested cells reduced damage. Phosphorylation inhibitory residues Cdc2, Thr14, Tyr15 coincided with inactivation after Interpretation this result, however, not straightforward due to regulation Thr14/Tyr15 phosphorylation feedback loops; hence, their can principle result merely inhibition activity. Consistent this, induced when kinase butyrolactone-I. Given these complications, we undertook more critical analysis mechanisms regulate Caffeine reversed damage-induced causing dephosphorylation still occurred even loops were blocked These data suggest part acts through independent activity, be accentuated protein phosphatases. The Wee1Hu unaltered phosphatase Cdc25C reduced. Thus, decrease may account for increase phosphorylation.