A single-site mutation in the XPAC gene alters photoproduct recognition.
A single-site mutation in the XPAC gene alters photoproduct recognition.
复制标题
XPAC 基因中的单点突变会改变光产物识别。
DOI：
10.1093/mutage/8.2.155
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发表时间：
1993
期刊：
影响因子：
2.7
通讯作者：
Cleaver,JE
中科院分区：
文献类型：
--
作者：
McDowell,ML;Nguyen,T;Cleaver,JE
XPAC（Xerodenna pigmentosum group A complementing）基因位于9号染色体上，在XP A组患者中携带多种点突变。我们研究了XPAC基因产物在切除修复中的作用，通过产生对紫外光具有增强抗性的XP A组细胞系（XP 12 RO）的回复突变体。这些细胞系之一，XP 129，可以正常修复（6-4）嘧啶-嘧啶酮光产物，但具有减少的修复环丁烷二聚体，如在XP 12 RO。XPAC基因的cDNA序列分析表明，XP 12 RO在氨基酸位置207处含有终止密码子，导致mRNA量减少，并且检测不到蛋白质。在回复突变体XP 129系中，该终止密码子已被进一步突变，并且现在在一个等位基因中编码甘氨酸而不是野生型精氨酸。通过等位基因特异性聚合酶链反应扩增检测到的mRNA水平大于链终止序列的回复序列。这些观察结果表明，点突变导致的错义突变在theXPAC基因和改变表达的XPAC蛋白可以改变切除修复系统的底物特异性，并暗示，XPAC基因产物在光产物识别中起着重要的作用。
TheXPAC(xerodenna pigmentosum group A complementing) gene, which is located on chromosome 9, carries a variety of point mutations in XP group A patients. We investigated the role of the XPAC gene product in excision repair by generating revertants of an XP group A cell line (XP12RO) that have increased resistance to ultraviolet light. One of these cell lines, XP129, can repair (6–4) pyrimidine-pyrimidone photoproducts normally but has reduced repair of cyclobutane dimers, as in XP12RO. Sequence analysis of cDNA from theXPACgene indicated that XP12RO contains a termination codon at amino acid position 207, resulting in a reduced amount of mRNA and no detectable protein. In the revertant XP129 line, this termination codon has been mutated further and now encodes giycine in one allele instead of the wild-type arginine. The mRNA level detected by allelespecific polymerase chain reaction amplification was greater for the reverted sequence than for the chain-terminating sequence. These observations indicated that a point mutation resulting in a mis-sense mutation in theXPACgene and altered expression of the XPAC protein can alter the substrate specificity of the excision repair system, and imply that the XPAC gene product plays an important role in photoproduct recognition.