XPD polymorphisms: effects on DNA repair proficiency
XPD polymorphisms: effects on DNA repair proficiency
复制标题
DOI：
10.1093/carcin/21.4.551
复制
发表时间：
2000-04-01
期刊：
影响因子：
4.7
通讯作者：
Bell, DA
中科院分区：
文献类型：
--
作者：
Lunn, RM;Helzlsouer, KJ;Bell, DA
XPD编码参与转录和核苷酸切除修复的DNA解旋酶。罕见的XPD突变减少了核苷酸切除修复，导致对紫外线过敏和皮肤癌风险增加。该基因中的几种多态性已被鉴定，但它们对DNA修复的影响尚不清楚。我们比较了XPD基因型在密码子312和751与DNA修复能力在31名妇女。采用PCR-RFLP方法检测XPD基因型，采用细胞遗传学方法检测X射线诱导的染色单体畸变（断裂和缺口），评估DNA修复能力。在37 ℃下孵育（照射后1.5 h）后，对每100个中期细胞的染色单体畸变进行评分，以修复DNA损伤。具有Lys/Lys密码子751 XPD基因型的个体比具有751 Gln等位基因的个体（34/100中期细胞）具有更高数量的染色单体畸变（132/100中期细胞）。具有大于60个染色单体断裂加缺口的个体被归类为具有次优修复。具有Lys/Lys 751基因型增加了次优DNA修复的风险（比值比7.2，95%置信区间= 1.01-87.7）。Asp 312 Asn XPD多态性似乎不影响DNA修复能力。这些结果表明，Lys 751（常见）等位基因可能会改变XPD蛋白产物，导致X射线诱导的DNA损伤的次优修复。
XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP, DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberrations were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys751 genotype increased the risk of sub-optimal DNA repair (odds ratio 7.2, 95% confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys751 (common) allele may alter the XPD protein product resulting in suboptimal repair of X-ray -induced DNA damage.