FEN1 cleaves displaced ssDNA flaps during MMEJ

Stable Identifier
Reaction [transition]
Homo sapiens
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DNA polymerase theta (POLQ) performs strand displacement DNA synthesis during microhomology-mediated end joining (MMEJ) (Kent et al. 2015), which is expected to result in the formation of displaced 5'-ssDNA flaps. FEN1, a 5'-flap endonuclease, is a necessary participant of MMEJ (Liang et al. 2005, Sharma et al. 2015). By analogy with base excision repair (Klungland and Lindahl 1997, Liu et al. 2005), FEN1 is thought to cleave the 5'-flaps generated by POLQ-mediated DNA strand displacement synthesis during MMEJ, thus enabling the subsequent ligation step.
Literature References
PubMed ID Title Journal Year
15561706 DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repair

Liu, Y, Beard, WA, Wilson, SH, Prasad, R, Hou, EW, Shock, DD

J. Biol. Chem. 2005
25789972 Homology and enzymatic requirements of microhomology-dependent alternative end joining

Srivastava, M, Javadekar, SM, Pandey, M, Sharma, S, Kumari, R, Raghavan, SC

Cell Death Dis 2015
16012167 Modulation of DNA end joining by nuclear proteins

Li, GC, Shao, C, Tischfield, JA, Deng, L, Chen, Y, Liang, L

J. Biol. Chem. 2005
25643323 Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase ?

McDevitt, SM, Chandramouly, G, Kent, T, Ozdemir, AY, Pomerantz, RT

Nat. Struct. Mol. Biol. 2015
9214649 Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1).

Lindahl, T, Klungland, A

EMBO J 1997
Catalyst Activity

5'-flap endonuclease activity of Extended microhomologous 3'-ssDNA overhangs-flap-DSB:MRN:RBBP8:FEN1 [nucleoplasm]

Orthologous Events
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