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. Author manuscript; available in PMC: 2018 Sep 1.
Published in final edited form as: Bioessays. 2017 Jul 13;39(9):10.1002/bies.201700077. doi: 10.1002/bies.201700077

Figure 4.

Figure 4

Proposed mechanism of large-scale GAA/TTC repeat expansion. Green = GAA repeats. Red = TTC repeats. A: Displacement synthesis by the lagging strand polymerase (Polδ) leads to the formation of a 5′ flap that can be processed by the flap endonuclease Fen1. B: In some circumstances (especially in the absence of Fen1) the displaced 5′ flap folds back, forming a triplex that blocks further synthesis by Polδ. C: Polδ switches template to the nascent leading strand in order to bypass the 5′ flap triplex and continue Okazaki fragment synthesis. D: Ligation of the extended Okazaki fragment to the folded back 5′ flap triplex resolves the template switching event and leads to a strand asymmetry that results in repeat expansion upon the next round of replication.