Tyrosyl-DNA-Phosphodiesterase

摘要: The abortive activity of DNA topoisomerase I (Top1) can lead to single-strand breaks with 3′-protein adducts termed Top1-DNA cleavage complexes. Repair these lesions in a prompt and accurate manner is essential for cell survival. One the cellular pathways repairing such involves tyrosyl-DNA phosphodiesterase 1 (Tdp1). Tdp1 hydrolyzes phosphodiester bond between tyrosine residue terminal 3′-phosphate DNA, type linkage found A mutation cause rare heredity neurodegenerative disease, spinocerebellar ataxia axonal neuropathy (SCAN1). Efforts elucidate mechanism Tdp1-depedent repair pathway have identified several other proteins, which form complex response network Tdp1. Conversely, structural biochemical studies suggest that act on broad spectrum 3′-phosphodiester linkages, potentially implicating pathways. In this chapter we summarize recent advances research concerning Tdp1, alternative Top1-induced damage, rational targeting as potential anticancer therapy.