An aromatic sensor with aversion to damaged strands confers versatility to DNA repair.

摘要: It was not known how xeroderma pigmentosum group C (XPC) protein, the primary initiator of global nucleotide excision repair, achieves its outstanding substrate versatility. Here, we analyzed molecular pathology a unique Trp690Ser substitution, which is only reported missense mutation in patients mapping to evolutionary conserved region XPC protein. The function this critical residue and neighboring aromatics tested by site-directed mutagenesis followed screening for activity DNA binding. This comparison demonstrated that Trp690 Phe733 drive preferential recruitment protein repair substrates mediating an exquisite affinity single-stranded sites. Such dual deployment aromatic side chains distinctive feature functional oligonucleotide/oligosaccharide-binding folds and, indeed, sequence homologies with replication A breast cancer susceptibility 2 indicate displays monomeric variant recurrent interaction motif. An aversion associate damaged oligonucleotides implies avoids direct contacts base adducts. These results reveal first time, our knowledge, entirely inverted mechanism recognition relies on detection configurations undamaged complementary double helix.