Attenuation of Mutation in the Mitochondrial Genome Through Supplementation of DNA Polymerase y Will Slow Aging-Related Decline of Function
Gradual decline of function can be attributed to the accumulation of mutations in mitochondrial DNA. These mutations arise due to imperfect proofreading by DNA polymerase y, a family A DNA polymerase and the only known mitochondrial exonuclease and replicase. As evidence exists for interchangeability of family A polymerases, this proposal suggests a method for confirming the possibility of interchanging or supplementing DNA polymerase y with E. coli DNA polymerase I. While both enzymes have exonucleolytic activity in the 3'->5' direction, E. coli DNA polymerase y contains an additional 5'->3' exonuclease domain that enhances its proofreading capacity. If the hypothesis is successfully upheld, it suggests a course of gene therapy that may be able to delay the onset at-symptoms of advanced aging in humans.
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