Figure 7.

Proposed Model for Role of TbPPL2 in Cell Proliferation

In all cells during every cell cycle, the DNA replication machinery will inevitably encounter abnormal or damaged DNA templates that result in the replication fork stalling. Replication can proceed despite these damaged templates by replication restart (shown on leading strand) or convergence of adjacent replicons. This will create a single-stranded gap opposite the damaged template. The proposed role of T. brucei PPL2 is to fill in these gaps using its TLS activity (green line), thus restoring the abnormal template in double-stranded DNA and facilitating its later repair. If PPL2-dependent damage tolerance does not operate, the postreplication gaps will persist and eventually form cytotoxic double-strand breaks (DSBs) in the DNA.