Structure-Function Studies Of DNA Replication Fidelity

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This year, our group published four scientific articles related to DNA replication and its fidelity. We showed that DNA polymerase delta has the predominant role in replication both the leading and the lagging strand during break-induced replication of chromosome ends. We showed that DNA polymerase delta also has key roles in leading strand DNA replication during initiation and during termination. We showed that during mitochondrial DNA replication, deletion mutations are formed at a significant frequency that is strongly increased by disease-associated mutations in the replicative DNA polymerase, Pol gamma. We solved the first ever X-ray crystal structure of DNA polymerase mu performing incorporation of a true double-strand DNA break relevant to nonhomologous end-joining of such breaks.