Institute Seminar

Dr William Copeland

Mitochondrial DNA Replication Group, National Institute of Environmental Health Sciences, USA

Structural insights into mitochondrial DNA mutagenesis


The human mitochondrial genome (mtDNA) encodes 37 genes, including 13 essential subunits of the oxidative phosphorylation system required for cellular ATP production. Mitochondrial DNA is replicated and maintained by a core replisome consisting of the DNA polymerase gamma, consisting of the catalytic POLG subunit and the POLG2 accessory, the Twinkle helicase, and the single stranded DNA binding protein.  Mutations in the genes encoding this replisome, cause depletion and deletion of the mitochondrial DNA, and are the most common causes of inherited mitochondrial disease affecting children and adults. To date, there are over 300 disease mutations in POLG that are linked to mitochondrial diseases such as myocerebrohepatopathy, Alpers-Huttenlocher syndrome, myoclonic epilepsy myopathy sensory ataxia, ataxia neuropathy spectrum and progressive external ophthalmoplegia.  Employing structural biology and biochemistry, we are investigating consequences of these disease mutations on the function of these enzymes and proteins. To understand the in vivo consequence from defective Pol gamma enzymes in patients with POLG mutations and how these defective polymerases form deletions, we have developed an ultrasensitive method for quantifying deletions in the mitochondrial genome.  The combined structural biology and bioinformatic analysis of mtDNA mutations is providing a comprehensive understanding of the mechanisms that causes mitochondrial diseases.

Information for Attendees

The Seminars are held in English, on-line using the ZOOM platform. The Seminars are open and all are welcome to attend. Duration: up to 40 minutes of presentation and 20 minutes of discussion.

When joining the meeting, please turn off the microphone and camera and use your full name as the participant’s identifier. After the presentation, it will be possible to ask questions via text communication (“chat” option) or audio communication (microphone).

Before joining the meeting, please read the Privacy Policy.

All Institute Seminars are held using the same Seminar Link.