Mutations of <i>GTBP</i> in Genetically Unstable Cells

DOI Web Site 22 Citations
  • Nickolas Papadopoulos
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Nicholas C. Nicolaides
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Bo Liu
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Ramon Parsons
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Christoph Lengauer
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Fabio Palombo
    Istituto di Richerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Italy.
  • Antonello D'Arrigo
    Istituto di Richerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Italy.
  • Sanford Markowitz
    Department of Medicine, Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA.
  • James K. V. Willson
    Department of Medicine, Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA.
  • Kenneth W. Kinzler
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
  • Josef Jiricny
    Istituto di Richerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Italy.
  • Bert Vogelstein
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.

Abstract

<jats:p> The molecular defects responsible for tumor cell hypermutability in humans have not yet been fully identified. Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 megabase of the related <jats:italic>hMSH2</jats:italic> gene on chromosome 2 and was found to be inactivated in three hypermutable cell lines. Unlike cells defective in other mismatch repair genes, which display widespread alterations in mononucleotide, dinucleotide, and other simple repeated sequences, the GTBP-deficient cells showed alterations primarily in mononucleotide tracts. These results suggest <jats:italic>GTBP</jats:italic> is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype. </jats:p>

Journal

  • Science

    Science 268 (5219), 1915-1917, 1995-06-30

    American Association for the Advancement of Science (AAAS)

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