Article
Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.
Nature communications - 27 Jun 2017
Tsutakawa Susan E, Thompson Mark J, Arvai Andrew S, Neil Alexander J, Shaw Steven J, Algasaier Sana I, Kim Jane C, Finger L David, Jardine Emma, Gotham Victoria J B, Sarker Altaf H, Her Mai Z, Rashid Fahad, Hamdan Samir M, Mirkin Sergei M, Grasby Jane A, Tainer John A
Abstract excerpt
DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5'-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5'-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the...
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