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Flap endonuclease 1 (FEN1), a RAD2 Class II nuclease, plays a crucial role in DNA repair, replication, and genomic stability.1 FEN1 removes the 5'-unannealed flap during Okazaki fragment processing in lagging strand DNA synthesis.2 Removal of the DNA flap is also critical in long-patch base excision repair and regulation of recombination.3 In yeast, FEN1 mutants display sensitivity to UV irradiation, deficient chromosome segregation, and cell cycle arrest in S phase.4 Furthermore, haploinsufficiency of FEN1 in mice leads to rapid tumor progression.4 FEN1 is overexpressed in many forms of cancer, including lung, gastric, prostate, pancreatic, brain, and breast.3
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1. The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-
2. Activity of FEN1 endonuclease on nucleosome substrates is dependent upon DNA sequence but not flap orientation. The Journal of Biological Chemisty 286(20), 17521-17529 (2011).
3. Complementary non-
4. Structural basis for recruitment of human flap endonuclease 1 to PCNA. EMBO J. 24(4), 683-693 (2005).