2005
DOI: 10.1038/nsmb981
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The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway

Abstract: The helicase-associated endonuclease for fork-structured DNA (Hef) is an archaeabacterial protein that processes blocked replication forks. Here we have isolated the vertebrate Hef ortholog and investigated its molecular function. Disruption of this gene in chicken DT40 cells results in genomic instability and sensitivity to DNA cross-links. The similarity of this phenotype to that of cells lacking the Fanconi anemia-related (FA) tumor-suppressor genes led us to investigate whether Hef functions in this pathwa… Show more

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Cited by 182 publications
(199 citation statements)
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“…Indeed, mutation of the endonuclease domain of FANCM in DT40 cells does not markedly affect crosslinker sensitivity (Mosedale et al 2005). However, FANCM does demonstrate an in vitro DNA-dependent ATPase function with an affinity for single-strand and forked structures that is lost when the helicase domain is mutated (Meetei et al 2005;Mosedale et al 2005). Mutation of the helicase domain also results in marked cisplatin sensitivity in DT40 cells.…”
Section: Fancm Is the Mammalian Ortholog Of Hefmentioning
confidence: 94%
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“…Indeed, mutation of the endonuclease domain of FANCM in DT40 cells does not markedly affect crosslinker sensitivity (Mosedale et al 2005). However, FANCM does demonstrate an in vitro DNA-dependent ATPase function with an affinity for single-strand and forked structures that is lost when the helicase domain is mutated (Meetei et al 2005;Mosedale et al 2005). Mutation of the helicase domain also results in marked cisplatin sensitivity in DT40 cells.…”
Section: Fancm Is the Mammalian Ortholog Of Hefmentioning
confidence: 94%
“…In contrast to bacterial Hef, the endonuclease domain of FANCM appears to be degenerate and nonfunctional (Meetei et al 2005). Indeed, mutation of the endonuclease domain of FANCM in DT40 cells does not markedly affect crosslinker sensitivity (Mosedale et al 2005). However, FANCM does demonstrate an in vitro DNA-dependent ATPase function with an affinity for single-strand and forked structures that is lost when the helicase domain is mutated (Meetei et al 2005;Mosedale et al 2005).…”
Section: Fancm Is the Mammalian Ortholog Of Hefmentioning
confidence: 97%
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“…A direct function of the FA pathway in DNA repair is further supported by Fancj being identical to the DNA helicase Brip1 (Brca1-interacting protein; refs. 10,35,36) and Fancm representing the human orthologue of the bacterial DNA repair protein Hef (11,37).…”
Section: Introductionmentioning
confidence: 99%