The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.

ABSTRACT: Polymorphisms and somatic mutations in Flap Endonuclease 1 (FEN1), an essential enzyme involved in DNA replication and repair, can lead to functional deficiencies of the FEN1 protein and a predisposition to cancer. We identified a FEN1 germline mutation that changed residue E359 to K in a patient whose family had a history of breast cancer. We determined that the E359K mutation, which is in the protein-protein domain of FEN1, abolished the interaction of FEN1 with Werner syndrome protein (WRN), an interaction that is critical for resolving stalled DNA replication forks. Furthermore, although the flap endonuclease activity of FEN1 E359K was unaffected, it failed to resolve bubble structures, which require the FEN1 gap-dependent endonuclease activity. To determine the etiological significanc

SUBMITTER: Chung L 

PROVIDER: S-EPMC4160428 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature