| First Author | Mori T | Year | 2019 |
| Journal | DNA Repair (Amst) | Volume | 80 |
| Pages | 52-58 | PubMed ID | 31279170 |
| Mgi Jnum | J:290960 | Mgi Id | MGI:6442186 |
| Doi | 10.1016/j.dnarep.2019.04.004 | Citation | Mori T, et al. (2019) High levels of oxidatively generated DNA damage 8,5'-cyclo-2'-deoxyadenosine accumulate in the brain tissues of xeroderma pigmentosum group A gene-knockout mice. DNA Repair (Amst) 80:52-58 |
| abstractText | Xeroderma pigmentosum (XP) is a genetic disorder associated with defects in nucleotide excision repair, a pathway that eliminates a wide variety of helix-distorting DNA lesions, including ultraviolet-induced pyrimidine dimers. In addition to skin diseases in sun-exposed areas, approximately 25% of XP patients develop progressive neurological disease, which has been hypothesized to be associated with the accumulation of an oxidatively generated type of DNA damage called purine 8,5'-cyclo-2'-deoxynucleoside (cyclopurine). However, that hypothesis has not been verified. In this study, we tested that hypothesis by using the XP group A gene-knockout (Xpa(-/-)) mouse model. To quantify cyclopurine lesions in this model, we previously established an enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (CdA-1) that specifically recognizes 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA). By optimizing conditions, we increased the ELISA sensitivity to a detection limit of one cyclo-dA lesion/10(6) nucleosides. The improved ELISA revealed that cyclo-dA lesions accumulate with age in the brain tissues of Xpa(-/-) and of wild-type (wt) mice, but there were significantly more cyclo-dA lesions in Xpa(-/-) mice than in wt mice at 6, 24 and 29 months of age. These findings are consistent with the long-standing hypothesis that the age-dependent accumulation of endogenous cyclopurine lesions in the brain may be critical for XP neurological abnormalities. |
