Figure 10.

Proposed roles for Pol α and PNCA in NHEJ. The figure presents a schematic overview of different NHEJ pathways described in the literature or identified in this study and characteristic intermediates of these pathways. A Ku-dependent pathway relying on the activities of DNA-PK, ligase IV/XRCC4 and MRE11 exonuclease is prominent in mammalian cells (53,60). This pathway appears to be branched, based on the requirement for DNA repair synthesis. A DNA synthesis-dependent pathway apparently requires Pol α activity to complete end joining whereas a DNA-independent pathway does not need any Pol activity. A Ku-independent pathway can be detected in many organisms in cases where the major pathway is defective or overloaded. This pathway may rely on the activities of Pol ɛ, FEN-1 and ligase III (74). Our results are consistent with a role of PCNA in this alternative pathway. See Discussion for details.