Abstract: The present disclosure provides polypeptides that have the ability to repair DNA damage by recognizing and removing a wide variety of DNA damage and distortions in double-stranded DNA. In particular, the polypeptides have the ability to remove cyclobutane pyrimidine dimers (CPDs) and/or (6-4) photoproducts from DNA. The polypeptides include at least one heterologous targeting sequence.

Abstract: Disclosed herein are methods of identifying small molecule compounds that are likely to be OGG1 inhibitors, kits that facilitate the performance of the methods, and methods of inhibiting OGG1 in vitro and in vivo.

Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.

Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL-inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Subjects in need of treatment with an ICL-inducing agent, include, for example, subjects diagnosed with a hyperproliferative disease, an autoimmune disease or an infectious disease. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent.

Abstract: Described herein are pyrimidine dimer-specific glycosylase (PDG) polypeptides and methods of use for repair of damaged DNA. The PDG polypeptides comprise amino acid sequence from T4-PDG, CV-PDG or engineered mutants thereof. The PDG polypeptides further comprise a targeting sequence, such as a nuclear targeting sequence or a mitochondrial targeting sequence, and a protein transduction domain. The mutant PDG polypeptides described herein retain at least some catalytic activity while exhibiting reduced cytotoxicity in wild-type cells.

Abstract: The present invention provides polypeptides having pyrimidine glycosylase activity, preferably, pyrimidine glycosylase/AP lyase activity. The polypeptides include a targeting sequence, preferably an exogenous target sequence. The invention includes polynucleotides that include a coding sequence encoding the polypeptides of the present invention. Also provided by the invention are methods of using the polypeptides.

Abstract: The present invention provides polypeptides having pyrimidine glycosylase activity, preferably, pyrimidine glycosylase/AP lyase activity. The polypeptides include a targeting sequence, preferably an exogenous target sequence. The invention includes polynucleotides that include a coding sequence encoding the polypeptides of the present invention. Also provided by the invention are methods of using the polypeptides.