Tdp2: a means to fixing the ends

• Published in: PLoS genetics Vol. 9; no. 3; p. e1003370
• Main Authors: Nitiss, John L, Nitiss, Karin C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-03-2013; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Cancer; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA repair; DNA Topoisomerases, Type II; Enzymes; Gene expression; Genomic Instability; Health aspects; Isomerases; Phosphate esters; Phosphoric Diester Hydrolases; Physiological aspects; Proteins; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003370

 
A key finding from the original identification of Tdp2 was that the protein was more active in processing 5' phosphotyrosyl-linked oligonucleotides, and that siRNA knockdown of Tdp2 in mammalian cells resulted in sensitivity to etoposide, a drug targeting topoisomerase II, but not camptothecin, a drug that targets topoisomerase I. Recent work has greatly enhanced our understanding of the biochemistry and structural biology of Tdp2. Since removal of Top2 will result in a double-strand break (DSB) (see Figure 1), the authors postulated that Tdp2 might function in concert with a specific DSB repair pathway. [...]Gómez-Herreros and colleagues were able to demonstrate the importance of Tdp2 in mice treated with etoposide.