Oxidative DNA damage protection
AssigneeUniversity of Massachusetts
InventorsMichael Volkert, Jen-Yeu Wang
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Abstract
Provided herein are methods of screening compounds, gene sequences, and gene products in bacteria for agents that are protective against oxidative DNA damage in a human or animal. Gene sequences identified by these screens can also be used in diagnostic assays that identify subjects at increased risk for oxidative DNA damage. Pharmaceutical compositions that include DNA protective agents identified by these screens are also provided.
Claims31
A method of identifying a candidate agent that is protective against oxidative DNA damage in a subject, the method comprising:
- (i) obtaining a mutator bacterial strain that (a) has a spontaneous mutation rate and (b) comprises a mutation reporter;
- (ii) contacting the mutator bacterial strain with a test compound;
- and
- (iii) evaluating the spontaneous mutation rate of the mutator strain;
- wherein a decrease in the spontaneous mutation rate indicates that the test compound is a candidate compound that is protective against oxidative DNA damage in a subject.
2 The method of claim 1, wherein the subject is a mammal.
A method of identifying a nucleic acid sequence that is protective against oxidative DNA damage, the method comprising:
- (i) obtaining a collection of nucleic acid molecules encoding a plurality of gene products;
- (ii) transforming the collection into a spontaneous mutator bacterial strain that (a) has a spontaneous mutation rate and (b) comprises a mutation reporter;
- and
- (iii) screening individual transformants for a decrease in the spontaneous mutation rate of the mutator strain;
- wherein a transformant that exhibits a decreased spontaneous mutation rate indicates that the nucleic acid sequence in the transformant is protective against oxidative damage.
An isolated polypeptide that (a) comprises amino acid residues 40-127 of SEQ ID NO:2 or amino acid residues 40-127 of SEQ ID NO:2 with 8 or fewer conservative amino acid substitutions;
- and (b) includes less than the full length sequence of SEQ ID NO:2.
Dependencies are inferred from the claim text.