Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells
Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells
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DOI：
10.1126/science.290.5489.138
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发表时间：
2000-10-06
期刊：
影响因子：
56.9
通讯作者：
Nikiforov, YE
中科院分区：
文献类型：
--
作者：
Nikiforova, MN;Stringer, JR;Nikiforov, YE
涉及RET基因的重排在放射相关的乳头状甲状腺癌(PTC)中很常见。RET/PTC1型重排是由RET和H4基因之间的非法重组所介导的10号染色体的倒位，这两个基因相距30兆碱基。这里我们问，尽管RET和H4之间有很大的线性距离，但它们在原子核中的接近是否会促进RET和H4的重组。我们使用双色荧光原位杂交和三维显微镜来定位RET和H4基因座在间期核中的位置。至少有一对RET和H4在35%的正常人甲状腺细胞和21%的外周血淋巴细胞中并存，但在正常乳腺上皮细胞中只有6%。RFT和H4的空间邻接性可能通过允许单个辐射轨迹在核中同一位置产生每个基因的双链断裂，从而为RET/PTC1重排的产生提供结构基础。
Rearrangements involving the RET gene are common in radiation-associated papillary thyroid cancer (PTC). The RET/PTC1 type of rearrangement is an inversion of chromosome 10 mediated by illegitimate recombination between the RET and the H4 genes, which are 30 megabases apart. Here we ask whether despite the great linear distance between them, RET;and H4 recombination might be promoted by their proximity in the nucleus. We used two-color fluorescence in situ hybridization and three-dimensional microscopy to map the positions of the RET and H4 loci within interphase nuclei. At least one pair of RET and H4 was juxtaposed in 35% of normal human thyroid cells and in 21% of peripheral blood lymphocytes, but only in 6% of normal mammary epithelial cells. Spatial contiguity of RFT and H4 may provide a structural basis for generation of RET/PTC1 rearrangement by allowing, a single radiation track to produce a double-strand break in each gene at the same site in the nucleus.