Flap endonucleases play a vital role in processing DNA. For example, Okazaki fragment maturation, base excision repair, and many other operations that are critical to maintaining genomic integrity require a properly functioning flap endonuclease. Extensive studies on human flap endonuclease-1 (FEN1) suggest that the L209D mutation, while distal from the active site, may allosterically control DNA recognition and subsequent binding by disrupting interactions between FEN1 and the 5’ flap. However, a detailed mechanism by which allosteric control could be achieved remains unknown and difficult to elucidate experimentally. Here, molecular dynamics simulation was used to investigate the allosteric effect of the L209D mutation on 5’ flap recognition and binding.

Molecular dynamics simulation of human flap endonuclease-1: L209D mutation allosterically modulates DNA binding and recognition

ACS Spring 2022

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