The NER apparatus excises DNA injury with surgical precision. XPA verifies the lesion and organizes the repair machinery around it, whereby the RPA complex stabilizes the open DNA configuration by binding to the non-damaged strand. In addition to the above global genome NER subpathway, specifically involving the XPC-hHR23B complex, a second NER process exists that accomplishes preferential and complete removal of lesions that block ongoing transcription. This transcription-coupled NER subpathway allows rapid resumption of the vital transcription process. Figure 2 Radiologic picture of a wt and TTD mouse mutant.
Mice are littermates.
Note the pronounced kyphosis, the general osteoporosis and the sclerosis of the skull. Importantly, the mice display cancer susceptibility, suggesting that patients may also have a hitherto unnoticed increased risk of developing cancer, consistent with the notion that DNA repair defects predispose to carcinogenesis. In addition, various signs of premature aging become apparent in the TTD mice. Thus, a combined defect in NER and transcription appears to induce early features of aging. This points to an important contribution of persisting DNA lesions to the features of the double mutant.