{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FBH1 is a UvrD‐family DNA helicase uniquely characterized by the presence of an F‐box domain that enables it to function both as a helicase and as a component of a ubiquitin ligase complex. Multiple studies have demonstrated that FBH1 localizes to sites of replication stress and DNA damage in a manner dependent on its helicase activity and interactions with single‐stranded DNA, where it plays a dual role in regulating homologous recombination. On one hand, FBH1 actively dismantles RAD51 nucleoprotein filaments—through its ssDNA translocase activity and via SCF complex–mediated ubiquitylation of RAD51—to restrain unscheduled and excessive recombination (for example, see"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " On the other hand, FBH1 contributes to proper processing of stalled replication forks by promoting endonucleolytic cleavage—through cooperation with nucleases such as MUS81—to generate double‐strand breaks that initiate appropriate checkpoint responses and, if damage is excessive, apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n FBH1’s functions extend to its regulation by other replication factors; its recruitment to replication factories is modulated by PCNA and is subsequently curtailed by targeted degradation via a CRL4(Cdt2)–PCNA pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, FBH1 is recognized as the human ortholog of the yeast Srs2 helicase, sharing an evolutionarily conserved role in preventing genomic instability by limiting aberrant recombination events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, proper FBH1 function is critical for mitotic fidelity; cells lacking FBH1, or expressing non‐degradable variants, display defective RAD51 localization and are hypersensitive to challenges that perturb chromosome decatenation, ultimately impacting anaphase segregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Importantly, the inactivation or deletion of FBH1 has been linked to pathological outcomes, as evidenced by melanoma cells that often harbor mutations or deletions in FBH1, thereby gaining a survival advantage under replication stress and promoting cellular transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore FBH1’s critical role in maintaining genomic stability by balancing homologous recombination and replication fork processing through its coordinated helicase and ubiquitin ligase activities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kasper Fugger, Martin Mistrik, Jannie Rendtlew Danielsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200812138"}], "href": "https://doi.org/10.1083/jcb.200812138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19736316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19736316"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jitka Simandlova, Jennifer Zagelbaum, Miranda J Payne, et al. 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