DNA Repair Has a New FAN1 Club Lara O'Donnell, Daniel Durocher  Molecular Cell  Volume 39, Issue 2, Pages 167-169 (July 2010) DOI: 10.1016/j.molcel.2010.07.010 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 Characterization of FAN1/KIAA1018 (A) Cartoon depicting the domain architecture of human FAN1. FAN1 contains a ubiquitin-binding domain (UBZ; yellow), a putative DNA-binding domain (SAP; green), and a VRR_nuclease domain (orange). Red arrows point to a plausible function for each domain. The UBZ domain is required for binding to the ubiquitylated ID complex (shown as blue and green ovals). (B) Nuclease activities of FAN1 and possible substrates. FAN1 is shown to possess an endonuclease activity with a strong affinity for 5′ FLAP structures and a potential weaker affinity for three-way junction structures (top row). For each structure, FAN1 is thought to cut at the double-stranded portion downstream of the branchpoint on the 5′ strand (black arrows). FAN1 also exhibits a 5′-3′ exonuclease activity on double-strand DNA (dsDNA) such as 5′ recessed dsDNA, nicked dsDNA, and gapped dsDNA (bottom row). (C) Possible role of FAN1 in ICL repair. In the presence of an ICL (red line), the FA core complex (orange) stimulates the monoubiquitylation and recruitment of the FA ID complex (blue and green) to the ICL. This may recruit FAN1 (pink), which, in combination with the MUS81 endonuclease (purple), may facilitate excision of the ICL, resulting in its unhooking. This, in turn, would promote translesion synthesis (TLS) and nucleotide excision repair (NER). Molecular Cell 2010 39, 167-169DOI: (10.1016/j.molcel.2010.07.010) Copyright © 2010 Elsevier Inc. Terms and Conditions