A naturally occurring genetic variant of human XRCC2 (R188H) confers increased resistance to cisplatin-induced DNA damage
- 作者：Patrick Danoy ; Eiichiro Sonoda ; Mark Lathrop ; Shunichi Takeda ; Fumihiko Matsuda
- 关键词：DNA repair gene ; Homologous recombination ; Single nucleotide polymorphism ; DT40 ; Cancer risk ; Cisplatin ; RAD51 ; XRCC2 ; XRCC3
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：19 January 2007
- 卷：352
- 期：3
- 页码：763-768
- 文件大小：403 K
摘要
Homologous recombination, a major double strand break repair pathway, plays critical roles in maintaining genome stability. Genetic polymorphisms in HR genes have been implicated in cancer risk. We report a novel assay system for evaluating polymorphisms in human homologous recombination genes using a panel of chicken DT40 repair mutants. We established mutant cell lines complemented with either wild-type or variant cDNAs of three human genes, RAD51, XRCC2, and XRCC3, and assessed their sensitivity to cisplatin and mitomycin C. DT40 mutants complemented with RAD51 coding and 5′UTR variants, and with a XRCC3 coding variant showed equivalent sensitivity as those with wild-type cDNAs. Interestingly, Xrcc2−/− DT40 cells complemented with variant XRCC2 (R188H) were more tolerant to cisplatin than those with wild-type XRCC2. Considering that the XRCC2 (R188H) allele reduces risk to epithelial ovarian cancer, the increased XRCC2 activity with the R188H polymorphism may have clinical benefit in preventing cancer risk.