Revoking the cellular license to replicate: yet another AAA assignment

Abstract

In this issue of Molecular Cell, Raman et al. (2011) and Franz et al. (2011) establish the AAA ATPase CDC-48/p97 as an essential regulator of eukaryotic DNA replication that coordinates the release of chromatin-bound CDT1 with its degradation by the proteasome.

Figure 1. Comparison of CDT1 degradation to the ERAD pathway

In ERAD, misfolded proteins undergo retrotranslocation through one of the few membrane complexes postulated to form retrotranslocation channels (blue cylinder). The process can be divided into three steps. 1) A ubiquitin ligase within a retrotranslocation complex conjugates ubiquitin chains to the substrate. 2) The p97/CDC48 complex that is recruited to the membrane via interacting with membrane receptors such as Derlin-1, VIMP, UbxD8, gp78 extracts ubiquitinated substrates from the membrane. 3) The p97/CDC48 complex acts with shuttling factors such as Ufd2, ataxin3, and ubiquilin to target dislocated substrates to the proteasome for degradation. The elimination of PCNA-bound CDT1 from the chromatin appears to follow the same suit, but the p97 receptors on the chromatin and the shuttling factors are unclear.