Subunit-specific degradation of the UmuD/D ' heterodimer by the ClpXP protease: the role of trans recognition in UmuD ' stability

The Escherichia coil UmuD' protein is a subunit of the recently described e rror-prone DNA polymerase, pol V, UmuD' is initially synthesized as an unst able and mutagenically inactive pro-protein, UmuD, Upon processing, UmuD' a ssumes a relatively stable conformation and becomes mutagenically active. W hile UmuD and UmuD' by themselves exist in vivo as homodimers, when togethe r they preferentially interact to form heterodimers. Quite strikingly, it i s in this context that UmuD' becomes susceptible to ClpXP-mediated proteoly sis. Here we report a novel targeting mechanism designed for degrading the mutagenically active UmuD' subunit of the UmuD/D' heterodimer complex, whil e leaving the UmuD protein intact. Surprisingly, a signal that is essential and sufficient for targeting UmuD' for degradation was found to reside on UmuD not UmuD', UmuD was also shown to be capable of channeling an excess o f UmuD' to ClpXP for degradation, thereby providing a mechanism. whereby ce lls can limit error-prone DNA replication.