Micronuclei in EM9 cells expressing polymorphic forms of human XRCC1
Micronuclei in EM9 cells expressing polymorphic forms of human XRCC1
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DOI：
10.1016/j.canlet.2004.08.013
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发表时间：
2005-04-18
期刊：
影响因子：
9.7
通讯作者：
Morimoto, K
中科院分区：
文献类型：
--
作者：
Qu, TL;Morii, E;Morimoto, K
x射线修复交叉互补基因1 （XRCC1）通过与其他碱基切除修复酶的相互作用参与碱基切除修复（BER）， XRCC1的多态性似乎会增加各种癌症的风险。我们利用微核试验评估了三种XRCC1多态性Arg194Trp、Arg280His和Arg399Gln对DNA损伤和修复程度的影响。含有野生型序列和三种多态性的XRCC1 cdna在缺乏执行XRCC1功能所需的完整序列的EM9细胞中过表达。正常人XRCC1 cDNA纠正了EM9细胞的缺陷。只有含有Arg399Gln多态性的XRCC1 cDNA不能完全纠正EM9细胞的DNA修复缺陷。这些结果表明，影响XRCC1修复DNA能力的是Arg399Gln多态性，而不是Arg194Trp或Arg280His多态性。本研究可能提供一个模型，可用于评估DNA修复基因多态性的功能意义。2004爱思唯尔爱尔兰有限公司版权所有。
X-ray repair cross-complementing gene 1 (XRCC1) is involved in base excision repair (BER) through interaction with other BER enzymes, and polymorphisms in XRCC1 appear to increase the risk of various cancers. We evaluated how three XRCC1 polymorphisms, Arg194Trp, Arg280His and Arg399Gln, affect the extent of DNA damage and repair using the micronucleus assay. XRCC1 cDNAs containing the wild-type sequence and the three polymorphisms were overexpressed in EM9 cells, which lack the full sequence needed to perform XRCC1 functions. Normal human XRCC1 cDNA corrected the defect in EM9 cells. Only XRCC1 cDNA containing the Arg399Gln polymorphism did not fully correct the DNA repair defect in EM9 cells. These results indicate that the Arg399Gln polymorphism, but not the Arg194Trp or Arg280His polymorphism, influences the ability of XRCC1 to repair DNA. This study may provide a model that can be used to evaluate the functional significance of polymorphisms in DNA repair genes. (c) 2004 Elsevier Ireland Ltd. All rights reserved.