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Published in final edited form as: Trends Biochem Sci. 2012 Jan 27;37(4):162–172. doi: 10.1016/j.tibs.2011.12.002

(a) FEN1 plays a crucial role in Okazaki fragment maturation during DNA lagging strand synthesis by removing flaps that contain the RNA primer ( ) of Okazaki fragments. The flaps are created by pol δ or pol ε strand-displacement synthesis. FEN1 usually captures a dual flap intermediate with a one-nucleotide 3′-flap along with a 5′-flap and removes the 5′-flap, leaving a nicked DNA that is a substrate for ligation, a “ligatable nick.” (b) During long-patch BER, FEN1 removes a modified (reduced or oxidized) sugar ( ) by either coordinating with pol β through the “Hit and Run” mechanism (the sub-pathway on the left) or capturing a 5′-flap associated with a modified sugar (the sub-pathway on the right) created by pol β or pol δ/ε. This latter process results in multi-nucleotide replacement. In the case where FEN1 cleavage results in a one-nucleotide gap, pol β will fill the gap readily leaving a ligatable nick.

Inline graphic — (a) FEN1 plays a crucial role in Okazaki fragment maturation during DNA lagging strand synthesis by removing flaps that contain the RNA primer ( ) of Okazaki fragments. The flaps are created by pol δ or pol ε strand-displacement synthesis. FEN1 usually captures a dual flap intermediate with a one-nucleotide 3′-flap along with a 5′-flap and removes the 5′-flap, leaving a nicked DNA that is a substrate for ligation, a “ligatable nick.” (b) During long-patch BER, FEN1 removes a modified (reduced or oxidized) sugar ( ) by either coordinating with pol β through the “Hit and Run” mechanism (the sub-pathway on the left) or capturing a 5′-flap associated with a modified sugar (the sub-pathway on the right) created by pol β or pol δ/ε. This latter process results in multi-nucleotide replacement. In the case where FEN1 cleavage results in a one-nucleotide gap, pol β will fill the gap readily leaving a ligatable nick.