Figure 4.

Full-length Polθ promotes MMEJ of long 3′ ssDNA overhangs. (A) Polθ-pol promotes snap-back replication on ssDNA by intramolecular microhomology search, transient microhomology annealing, and subsequent extension of the minimally paired 3′ terminal end of ssDNA. This activity suppresses MMEJ of long ssDNA overhangs by Polθ-pol. (B) Full-length Polθ performs MMEJ of long ssDNA. Covalent attachment of Polθ-hel to Polθ-pol through the Polθ central domain or a short peptide linker suppresses intramolecular microhomology search and snap-back replication, which results in promoting intermolecular microhomology search and subsequent MMEJ.