Mechanistic Studies of Cancer Associated Polymerase Mutations Using Yeast Pols Delta and Epsilon

Speaker Name: 
Joe Dahl, Ph.D.
Speaker Title: 
Postdoctoral Researcher
Speaker Organization: 
Genome integrity and Structural Biology Lab at the National Institute of Environmental Health Sciences, Durham, NC
Start Time: 
Thursday, February 27, 2020 - 4:00pm
End Time: 
Thursday, February 27, 2020 - 5:00pm


A myriad of DNA polymerase mutations have been associated with human disease. Mutations in human POLE and POLD have been identified in cancers derived from all tissues. It is believed that many of the mutations in the protein products of these genes, Pols Epsilon and Delta respectively, are drivers of hypermutation in some tumors. The proposed mutator phenotype suggests the amino acid substitutions associated with these mutations are structurally and or functionally significant. Here we present ongoing mechanistic studies into several of these mutations. This work uses cancer as a tool to identify functionally significant residues to direct mechanistic research into DNA polymerases. The data demonstrate that cancer associated mutations in Pols Epsilon and Delta can alter the activities of these replicases through multiple mechanisms. These findings support clinical research into personalized medicine and chemotherapeutic treatment.


Joe Dahl is a Postdoctoral Fellow at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. Joe joined the Genome integrity Structural Biology Lab at the NIEHS to train in Dr. Tom Kunkel's DNA Replication Fidelity Group in 2016. His research focuses on mechanistic studies of the major eukaryotic DNA Replicases, Polymerases Epsilon and Delta, and also includes studies of ribonucleotide incorporation into the genome during DNA replication. As a fellow at the NIEHS Joe was nominated president of the NIEHS Trainees' Assembly (NTA) Steering Committee; during which his goals have been to enhance trainees' experiences, develop a stronger culture of collaboration and increase engagement by international fellows who train at the NIEHS.

All are welcome to join us for this Pathways to Careers in Genomics talk. Talk will be approximately 60 minutes with 30 minutes for discussion to follow.

To accommodate a disability, please contact Ben Coffey at the UC Santa Cruz Genomics Institute (, 831-459-1477).

Sponsored by the Genomics Institute Office of Diversity

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