Model for repair of polymerase alpha-incorporated mismatches and completion of Okazaki fragment processing. First, the DNA polymerase alpha/primase complex makes a RNA primer (hatched line) and begins DNA synthesis, and then FEN1 removes the initiator RNA, perhaps including some DNA as well, with or without extension from an upstream fragment. Meanwhile, DNA polymerase alpha continues DNA synthesis and inserts a mismatch that slightly disrupts the DNA helix. This disruption promotes the removal of the mismatch by FEN1 in one cut or a series of endonucleolytic cuts, depending on the location of the mismatch. After synthesizing 10-20 nucleotides, DNA polymerase alpha is replaced by DNA polymerase delta or epsilon for processive synthesis. The upstream fragment is extended up to the downstream fragment, and ligation occurs. If DNA polymerase alpha does not incorporate a mismatch, unnecessary cleavage by FEN1 is minimized, and ligation ensues immediately after RNA removal.
From: J. A. Rumbaugh, L. A. Henricksen, M. S. DeMott, and R.A. Bambara (1999) Cleavage of Substrates with Mismatched Nucleotides by Flap Endonuclease-1, J Biol Chem. 274, 14602-14608.