FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts

Timothy B. C. London, Louise J. Barber, Georgina Mosedale, Gavin P. Kelly, Shankar Balasubramanian, Ian D. Hickson, Simon J. Boulton, Kevin Hiom (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    140 Citations (Scopus)

    Abstract

    Fanconi anemia (FA) is a heritable human cancer-susceptibility disorder, delineating a genetically heterogenous pathway for the repair of replication-blocking lesions such as interstrand DNA cross-links. Here we demonstrate that one component of this pathway, FANCJ, is a structure-specific DNA helicase that dissociates guanine quadruplex DNA (G4 DNA) in vitro. Moreover, in contrast with previously identified G4 DNA helicases, such as the Bloom's helicase (BLM), FANCJ unwinds G4 substrates with 5'-3' polarity. In the FA-J human patient cell line EUFA0030 the loss of FANCJ G4 unwinding function correlates with the accumulation of large genomic deletions in the vicinity of sequences, which match the G4 DNA signature. Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication.

    Original languageEnglish
    Pages (from-to)36132-36139
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume283
    Issue number52
    DOIs
    Publication statusPublished - 26 Dec 2008

    Keywords

    • Basic-Leucine Zipper Transcription Factors
    • Binding, Competitive
    • Cell Line
    • Cell Line, Tumor
    • Cross-Linking Reagents
    • DNA Helicases
    • DNA Replication
    • Fanconi Anemia Complementation Group Proteins
    • G-Quadruplexes
    • Gene Deletion
    • Genetic Predisposition to Disease
    • Genome
    • Humans
    • Nucleic Acid Conformation
    • Nucleic Acid Hybridization
    • RecQ Helicases

    Cite this

    London, T. B. C., Barber, L. J., Mosedale, G., Kelly, G. P., Balasubramanian, S., Hickson, I. D., ... Hiom, K. (2008). FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. Journal of Biological Chemistry, 283(52), 36132-36139. https://doi.org/10.1074/jbc.M808152200
    London, Timothy B. C. ; Barber, Louise J. ; Mosedale, Georgina ; Kelly, Gavin P. ; Balasubramanian, Shankar ; Hickson, Ian D. ; Boulton, Simon J. ; Hiom, Kevin. / FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 52. pp. 36132-36139.
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    London, TBC, Barber, LJ, Mosedale, G, Kelly, GP, Balasubramanian, S, Hickson, ID, Boulton, SJ & Hiom, K 2008, 'FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts', Journal of Biological Chemistry, vol. 283, no. 52, pp. 36132-36139. https://doi.org/10.1074/jbc.M808152200

    FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. / London, Timothy B. C.; Barber, Louise J.; Mosedale, Georgina; Kelly, Gavin P.; Balasubramanian, Shankar; Hickson, Ian D.; Boulton, Simon J.; Hiom, Kevin (Lead / Corresponding author).

    In: Journal of Biological Chemistry, Vol. 283, No. 52, 26.12.2008, p. 36132-36139.

    Research output: Contribution to journalArticle

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    AU - Balasubramanian, Shankar

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    AU - Hiom, Kevin

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    KW - Gene Deletion

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    KW - Humans

    KW - Nucleic Acid Conformation

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    KW - RecQ Helicases

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    JO - Journal of Biological Chemistry

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    ER -

    London TBC, Barber LJ, Mosedale G, Kelly GP, Balasubramanian S, Hickson ID et al. FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. Journal of Biological Chemistry. 2008 Dec 26;283(52):36132-36139. https://doi.org/10.1074/jbc.M808152200