AlpersHuttenlocher Syndrome POLG Aaron Burd AlpersHuttenlocher Syndrome What
Alpers-Huttenlocher Syndrome (POLG) Aaron Burd
• Alpers-Huttenlocher Syndrome
What is Alpers-Huttenlocher Syndrome? Also known as Alpers Disease Autosomal Recessive Mutation on POLG gene responsible Neurodegenerative Disease http: //alpersawareness. org/wordpress/wp-content/uploads/2012/05/Logan. jpg Most common cause of death is Liver Failure
What gene is affected by Alpers-Huttenlocher? aka DNA Polymerase gamma Located on Chromosome 15 Encodes for a single alpha subunit DNA polymerase gamma activity located in the mitochondria mt. DNA replication is most affected POLG
What protein does POLG encode? Alpha Subunit Makes up the DNA polymerase gamma complex Single Amino Acid Change causes the mutation Only one function able region on protein
Mitochondrial DNA http: //en. wikipedia. org/wiki/Mitochondrial_DNA#/media/File: Mitochondrial_DNA_en. svg
How conserved is the protein sequence? Human Mouse Gorilla Dog Bonobo Elephant Anole Alpaca Hedgehog Marmoset Medaka 871 578 871 873 632 854 836 781 1175 861 834 274 274 323 274 241 274 274
Phylogenetic Trees
Gene Ontology POLG Molecular Functions: • Protease binding • Nucleic acid binding • DNA binding • Chromatin binding • DNA-directed DNA polymerase activity • Exonuclease activity • Nucleotidyltransferase activity • Protein binding POLG Cellular Components: • Gamma DNA polymerase complex • Mitochondria nucleoid • Extracellular exosome Biological Processes: • mt. DNA Replication • Aging • DNA biosynthetic process • DNA metabolic process • Base excision repair; gap filling
POLG Interactions
Primary Goal To obtain a better and more complete understanding how the POLG gene affects the mitochondria and the human body overall.
Hypothesis f the α subunit protein so that it becomes non functioning and unsuccessful in binding to the other
AIM 1 Identifying molecules that interact with the protein is extremely useful in determining the reasons we have our disease phenotype. One such way we can test this is through Small Molecule assays.
AIM 2 Alpha Subunit We will study the protein interactions within the protein polymerase γ and how they will affect the function of mt. DNA replication. Specifically we will look at the α subunit by using Tap-tag assays paired with Mass Spectrometry.
Future Implications • More effective treatments • Possible Rescue • Mitochondrial DNA research
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