Papadopoulos N, Nicolaides N C, Liu B, Parsons R, Lengauer C, Palombo F, D'Arrigo A, Markowitz S, Willson J K, Kinzler K W
Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
Science. 1995 Jun 30;268(5219):1915-7. doi: 10.1126/science.7604266.
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 hMSH2 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 that GTBP is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype.
导致人类肿瘤细胞超突变性的分子缺陷尚未完全明确。在此，编码G/T错配结合蛋白（GTBP）的基因被定位到2号染色体上相关的hMSH2基因的1兆碱基范围内，并发现其在三个超突变细胞系中失活。与其他错配修复基因有缺陷的细胞不同，后者在单核苷酸、二核苷酸和其他简单重复序列中表现出广泛的改变，而GTBP缺陷的细胞主要在单核苷酸序列中出现改变。这些结果表明，GTBP对于维持人类基因组的完整性很重要，并证明了导致突变体表型变异的分子缺陷。
