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Busygina, V., Suphapeetiporn, K., Marek, L.R., Stowers, R.S., Xu, T., Bale, A.E. (2004). Hypermutability in a Drosophila model for multiple endocrine neoplasia type 1.  Hum. Mol. Genet. 13(20): 2399--2408.
FlyBase ID
FBrf0180339
Publication Type
Research paper
Abstract

Multiple endocrine neoplasia type I (MEN1) is an autosomal dominant cancer predisposition syndrome, the gene for which encodes a nuclear protein, menin. The biochemical function of this protein has not been completely elucidated, but several studies have shown a role in transcriptional modulation through recruitment of histone deacetylase. The mechanism by which MEN1 mutations cause tumorigenesis is unknown. The Drosophila homolog of MEN1, Mnn1, encodes a protein 50% identical to human menin. In order to further elucidate the function of MEN1, we generated a null allele of this gene in Drosophila and showed that homozygous inactivation results in morphologically normal flies that are hypersensitive to ionizing radiation and two DNA cross-linking agents, nitrogen mustard and cisplatinum. The spectrum of agents to which mutant flies are sensitive and analysis of the molecular mechanisms of this sensitivity suggest a defect in nucleotide excision repair. Drosophila Mnn1 mutants have an elevated rate of both sporadic and DNA damage-induced mutations. In a genetic background heterozygous for lats, a Drosophila and vertebrate tumor suppressor gene, homozygous inactivation of Mnn1 enhanced somatic mutation of the second allele of lats and formation of multiple primary tumors. Our data indicate that Mnn1 is a novel member of the class of autosomal dominant cancer genes that function in maintenance of genomic integrity, similar to the BRCA and HNPCC genes.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Hum. Mol. Genet.
    Title
    Human Molecular Genetics
    Publication Year
    1992-
    ISBN/ISSN
    0964-6906
    Data From Reference
    Aberrations (2)
    Alleles (11)
    Genes (6)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (1)
    Transgenic Constructs (3)