Involvement of MRE11A and XPA gene polymorphisms in the modulation of DNA double-strand break repair activity: A genotype-phenotype correlation study
Involvement of MRE11A and XPA gene polymorphisms in the modulation of DNA double-strand break repair activity: A genotype-phenotype correlation study
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DOI：
10.1016/j.dnarep.2011.08.003
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发表时间：
2011-10-10
期刊：
影响因子：
3.8
通讯作者：
Matullo, Giuseppe
中科院分区：
文献类型：
--
作者：
Ricceri, Fulvio;Porcedda, Paola;Matullo, Giuseppe
DNA double-strand breaks (DSB) are the most lethal form of ionizing radiation-induced DNA damage, and failure to repair them results in cell death. In order to see if any associations exist between DNA repair gene polymorphisms and phenotypic profiles of DSB repair (DSBR) we performed a genotype-phenotype correlation study in 118 young healthy subjects (mean age 25.8 +/- 6.7 years). Subjects were genotyped for 768 single nucleotide polymorphisms (SNPs) with a custom Illumina Golden Gate Assay, and an H2AX histone phosphorylation assay was done to test DSBR capacity.We found that H2AX phosphorylation at 1 h was significantly lower in subjects heterozygous (no variant homozygotes were observed) for the XPA gene SNP rs3176683 (p-value = 0.005), while dephosphorylation was significantly higher in subjects carrying the variant allele in three MRE11A gene SNPs: rs1014666, rs476137 and rs2508784 (p-value = 0.003, 0.003 and 0.008, respectively). An additive effect of low-activity DNA repair alleles was associated with altered DSBR activity, as demonstrated by both H2AX phosphorylation at I h (p-trend
