FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells

Hiroyuki Kitao, Indrajit Nanda, Ryuichi P. Sugino, Aiko Kinomura, Mitsuyoshi Yamazoe, Hiroshi Arakawa, Michael Schmid, Hideki Innan, Kevin Hiom, Minoru Takata

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Defects in the FANCJ/BRIP1 helicase gene are associated with genome instability disorders such as familial breast cancer or Fanconi anemia (FA). Although FANCJ has an in vitro activity to resolve G-quadruplex (G4) structures, and FANCJ ortholog in C. elegans prevents G4-associated deletions during replication, how FANCJ loss affects genome integrity in higher organisms remains unclear. Here, we report that FANCJ, but not other FA genes FANCD2 or FANCC, protected against large-scale genomic deletion that occurred frequently at the rearranged immunoglobulin heavy chain (IgH) locus in chicken DT40 cell line, suggesting that FancJ protects the genome independently of the FA ubiquitination pathway. In a more unbiased approach using array-comparative genomic hybridization, we identified de novo deletions as well as amplifications in fancj cells kept in culture for 2 months. A cluster of G4 sequence motifs was found near the breakpoint of one amplified region, but G4 sequence motifs were not detected at the breakpoints of two deleted regions. These results collectively suggest that, unlike in C. elegans, actions of vertebrate FANCJ to promote genome stability may not be limited to protection against the G4-mediated gene deletions.

    Original languageEnglish
    Pages (from-to)714-727
    Number of pages14
    JournalGenes to Cells
    Volume16
    Issue number6
    DOIs
    Publication statusPublished - Jun 2011

    Keywords

    • CROSS-LINK REPAIR
    • IMMUNOGLOBULIN GENE CONVERSION
    • FANCONI-ANEMIA PATHWAY
    • DNA-REPAIR
    • HOMOLOGOUS RECOMBINATION
    • BREAST-CANCER
    • MONOUBIQUITINATED FANCD2
    • BACH1
    • IDENTIFICATION
    • NUCLEASE

    Cite this

    Kitao, H., Nanda, I., Sugino, R. P., Kinomura, A., Yamazoe, M., Arakawa, H., ... Takata, M. (2011). FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. Genes to Cells, 16(6), 714-727. https://doi.org/10.1111/j.1365-2443.2011.01523.x
    Kitao, Hiroyuki ; Nanda, Indrajit ; Sugino, Ryuichi P. ; Kinomura, Aiko ; Yamazoe, Mitsuyoshi ; Arakawa, Hiroshi ; Schmid, Michael ; Innan, Hideki ; Hiom, Kevin ; Takata, Minoru. / FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. In: Genes to Cells. 2011 ; Vol. 16, No. 6. pp. 714-727.
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    abstract = "Defects in the FANCJ/BRIP1 helicase gene are associated with genome instability disorders such as familial breast cancer or Fanconi anemia (FA). Although FANCJ has an in vitro activity to resolve G-quadruplex (G4) structures, and FANCJ ortholog in C. elegans prevents G4-associated deletions during replication, how FANCJ loss affects genome integrity in higher organisms remains unclear. Here, we report that FANCJ, but not other FA genes FANCD2 or FANCC, protected against large-scale genomic deletion that occurred frequently at the rearranged immunoglobulin heavy chain (IgH) locus in chicken DT40 cell line, suggesting that FancJ protects the genome independently of the FA ubiquitination pathway. In a more unbiased approach using array-comparative genomic hybridization, we identified de novo deletions as well as amplifications in fancj cells kept in culture for 2 months. A cluster of G4 sequence motifs was found near the breakpoint of one amplified region, but G4 sequence motifs were not detected at the breakpoints of two deleted regions. These results collectively suggest that, unlike in C. elegans, actions of vertebrate FANCJ to promote genome stability may not be limited to protection against the G4-mediated gene deletions.",
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    author = "Hiroyuki Kitao and Indrajit Nanda and Sugino, {Ryuichi P.} and Aiko Kinomura and Mitsuyoshi Yamazoe and Hiroshi Arakawa and Michael Schmid and Hideki Innan and Kevin Hiom and Minoru Takata",
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    Kitao, H, Nanda, I, Sugino, RP, Kinomura, A, Yamazoe, M, Arakawa, H, Schmid, M, Innan, H, Hiom, K & Takata, M 2011, 'FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells', Genes to Cells, vol. 16, no. 6, pp. 714-727. https://doi.org/10.1111/j.1365-2443.2011.01523.x

    FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. / Kitao, Hiroyuki; Nanda, Indrajit; Sugino, Ryuichi P.; Kinomura, Aiko; Yamazoe, Mitsuyoshi; Arakawa, Hiroshi; Schmid, Michael; Innan, Hideki; Hiom, Kevin; Takata, Minoru.

    In: Genes to Cells, Vol. 16, No. 6, 06.2011, p. 714-727.

    Research output: Contribution to journalArticle

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    AU - Kitao, Hiroyuki

    AU - Nanda, Indrajit

    AU - Sugino, Ryuichi P.

    AU - Kinomura, Aiko

    AU - Yamazoe, Mitsuyoshi

    AU - Arakawa, Hiroshi

    AU - Schmid, Michael

    AU - Innan, Hideki

    AU - Hiom, Kevin

    AU - Takata, Minoru

    PY - 2011/6

    Y1 - 2011/6

    N2 - Defects in the FANCJ/BRIP1 helicase gene are associated with genome instability disorders such as familial breast cancer or Fanconi anemia (FA). Although FANCJ has an in vitro activity to resolve G-quadruplex (G4) structures, and FANCJ ortholog in C. elegans prevents G4-associated deletions during replication, how FANCJ loss affects genome integrity in higher organisms remains unclear. Here, we report that FANCJ, but not other FA genes FANCD2 or FANCC, protected against large-scale genomic deletion that occurred frequently at the rearranged immunoglobulin heavy chain (IgH) locus in chicken DT40 cell line, suggesting that FancJ protects the genome independently of the FA ubiquitination pathway. In a more unbiased approach using array-comparative genomic hybridization, we identified de novo deletions as well as amplifications in fancj cells kept in culture for 2 months. A cluster of G4 sequence motifs was found near the breakpoint of one amplified region, but G4 sequence motifs were not detected at the breakpoints of two deleted regions. These results collectively suggest that, unlike in C. elegans, actions of vertebrate FANCJ to promote genome stability may not be limited to protection against the G4-mediated gene deletions.

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    KW - IMMUNOGLOBULIN GENE CONVERSION

    KW - FANCONI-ANEMIA PATHWAY

    KW - DNA-REPAIR

    KW - HOMOLOGOUS RECOMBINATION

    KW - BREAST-CANCER

    KW - MONOUBIQUITINATED FANCD2

    KW - BACH1

    KW - IDENTIFICATION

    KW - NUCLEASE

    U2 - 10.1111/j.1365-2443.2011.01523.x

    DO - 10.1111/j.1365-2443.2011.01523.x

    M3 - Article

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    SP - 714

    EP - 727

    JO - Genes to Cells

    JF - Genes to Cells

    SN - 1356-9597

    IS - 6

    ER -

    Kitao H, Nanda I, Sugino RP, Kinomura A, Yamazoe M, Arakawa H et al. FancJ/Brip1 helicase protects against genomic losses and gains in vertebrate cells. Genes to Cells. 2011 Jun;16(6):714-727. https://doi.org/10.1111/j.1365-2443.2011.01523.x