GTBP, a 160-Kilodalton Protein Essential for Mismatch-binding Activity in Human Cells
Fabio Palombo(Institute of Molecular Biology and Pathology), Paola Gallinari(Institute of Molecular Biology and Pathology), Ingram Iaccarino(Institute of Molecular Biology and Pathology), Teresa Lettieri(Institute of Molecular Biology and Pathology), Melya J. Hughes(Institute of Molecular Biology and Pathology), Antonello D’Arrigo(Institute of Molecular Biology and Pathology), Oanh Truong(Ludwig Cancer Research), J. Justin Hsuan(Ludwig Cancer Research), Josef Jiricny(Institute of Molecular Biology and Pathology)
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Abstract
DNA mismatch recognition and binding in human cells has been thought to be mediated by the hMSH2 protein. Here it is shown that the mismatch-binding factor consists of two distinct proteins, the 100-kilodalton hMSH2 and a 160-kilodalton polypeptide, GTBP (for G/T binding protein). Sequence analysis identified GTBP as a new member of the MutS homolog family. Both proteins are required for mismatch-specific binding, a result consistent with the finding that tumor-derived cell lines devoid of either protein are also devoid of mismatch-binding activity.
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