FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain

Simon Pennell (Lead / Corresponding author), Anne-Cécile Déclais, Jiejin Li, Lesley F. Haire, Wioletta Berg, José W. Saldanha, Ian A. Taylor, John Rouse, David M. J. Lilley, Stephen J. Smerdon

    Research output: Contribution to journalArticle

    9 Citations (Scopus)
    185 Downloads (Pure)

    Abstract

    FAN1 is a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. It is the only eukaryotic protein with a virus-type replication-repair nuclease ("VRR-Nuc") "module" that commonly occurs as a standalone domain in many bacteria and viruses. Crystal structures of three representatives show that they structurally resemble Holliday junction resolvases (HJRs), are dimeric in solution, and are able to cleave symmetric four-way junctions. In contrast, FAN1 orthologs are monomeric and cleave 5' flap structures in vitro, but not Holliday junctions. Modeling of the VRR-Nuc domain of FAN1 reveals that it has an insertion, which packs against the dimerization interface observed in the structures of the viral/bacterial VRR-Nuc proteins. We propose that these additional structural elements in FAN1 prevent dimerization and bias specificity toward flap structures.
    Original languageEnglish
    Pages (from-to)84-93
    Number of pages10
    JournalCell Reports
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 10 Jul 2014

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