Characterization of Two Novel Mutants of DNA Polymerase Delta in Drosophila melanogaster

Abstract

DNA is the genetic material for all living organisms which is constantly being unpackaged, replicated and repackaged. The replication of this genetic material involves numerous different proteins; however, DNA polymerase delta (pol [delta]) carries much of the load by replicating a major portion of the genome in both leading and lagging strand synthesis. Using the model organism, Drosophila melanogaster, we investigate two novel mutations in two different evolutionary conserved regions. One region corresponds with the polymerase's ability to polymerize new nucleotides onto an existing strand of DNA. The other region corresponds with the polymerase's ability to proofread in the 3' to 5' direction. These two mutants, both homozygous lethal and recessive, show interesting phenotypes with a delay in S-phase, numerous chromosome aberrations, defects in endoreplication and possible protection form DNA damage. Using these two mutants, these two domains can be further characterized. By understanding how pol [delta] functions in an in vivo setting, we can apply this knowledge to the mechanics of cancer biology in humans, another multicelluar organism, and inform new therapies to treat it.