DNA Repair

DNA repair inhibitors and activators act on enzymes that detect and fix damaged bases and broken strands. A 1993 review estimated that hydrolysis and oxidation damage thousands of DNA bases in every cell each day. In base excision repair, 8-oxoguanine DNA glycosylase 1 (OGG1) excises oxidized guanine, and apurinic/apyrimidinic endonuclease 1 (APE1) then cuts the abasic site. TH10785 is listed as an OGG1 activator, whereas APE1-IN-1 inhibits APE1. DNA repair protein RAD52 homolog (RAD52) became a target after a 2011 study found its loss lethal in cells lacking breast cancer susceptibility protein 2 (BRCA2). D-I03 inhibits RAD52, HAMNO blocks replication protein A (RPA), and CD00509 inhibits tyrosyl-DNA phosphodiesterase 1 (TDP1).

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