biostudies-literatureLuebben SWNCI NIH HHS10283-97https://www.ebi.ac.uk/biostudies/studies/S-EPMC3905894biostudies-literatureUnknown41(22)HELQ is a superfamily 2 DNA helicase found in archaea and metazoans. It has been implicated in processing stalled replication forks and in repairing DNA double-strand breaks and inter-strand crosslinks. Though previous studies have suggested the possibility that HELQ is involved in the Fanconi anemia (FA) pathway, a dominant mechanism for inter-strand crosslink repair in vertebrates, this connection remains elusive. Here, we investigated this question in mice using the Helq(gt) and Fancc(-) strains. Compared with Fancc(-)(/)(-) mice lacking FANCC, a component of the FA core complex, Helq(gt/gt) mice exhibited a mild of form of FA-like phenotypes including hypogonadism and cellular sensitivity to the crosslinker mitomycin C. However, unlike Fancc(-)(/)(-) primary fibroblasts, Helq(gt/gt) ceNucleic acids researchHelq acts in parallel to Fancc to suppress replication-associated genome instability.PMC3905894R01CA148806P30 CA077598R01 CA148806Akre MKO'Sullivan MGShima NKawabata TJohnson CSLuebben SWLee WLfalseHelq acts in parallel to Fancc to suppress replication-associated genome instability.HELQ is a superfamily 2 DNA helicase found in archaea and metazoans. It has been implicated in processing stalled replication forks and in repairing DNA double-strand breaks and inter-strand crosslinks. Though previous studies have suggested the possibility that HELQ is involved in the Fanconi anemia (FA) pathway, a dominant mechanism for inter-strand crosslink repair in vertebrates, this connection remains elusive. Here, we investigated this question in mice using the Helq(gt) and Fancc(-) strains. Compared with Fancc(-)(/)(-) mice lacking FANCC, a component of the FA core complex, Helq(gt/gt) mice exhibited a mild of form of FA-like phenotypes including hypogonadism and cellular sensitivity to the crosslinker mitomycin C. However, unlike Fancc(-)(/)(-) primary fibroblasts, Helq(gt/gt) ce2013-01-01T00:00:00Z2013 Dec2025-04-22T19:28:36.47Z2019-03-27T01:20:51ZS-EPMC39058942400504110.1093/nar/gkt676