Líffræðifélag Íslands
Líffræðiráðstefnan 2015

Erindi/veggspjald / Talk/poster V74

The Role of ALKBH3 in Epigenetics, DNA Repair, and Breast Cancer

Ólafur Andri Stefánsson, Þorkell Guðjónsson, Jórunn Eyfjörð, Stefán Sigurðsson

1. Háskóli Íslands, 2. Læknadeild

Kynnir / Presenter: Stefán Þór Hermanowicz

Tengiliður / Corresponding author: Stefán Þór Hermanowicz (sthh16@hi.is)

DNA repair is crucial to maintaining the health and integrity of cells. Damage that is allowed to persist within the DNA may aid in the formation of diseases such as cancer. It is therefore crucial that proteins involved in DNA repair are functional. Incidences where proper protein expression is impaired have been linked to disease formation. Epigenetic modification, particularly promoter methylation can cause a downregulation of gene expression. Through database analysis we identified 5 repair proteins which undergo promoter methylation, one of which being ALKBH3. ALKBH3 is a protein responsible for the repair of a form of DNA alkylation damage, specifically 3-methyl-cytosine. According to The Cancer Genome Atlas, 20% of breast cancers are undergoing promoter methylation for ALKBH3. Within Iceland we have found the incidence rate to be 5-10% of breast cancer samples. Importantly, this epigenetic silencing is occurring within tumors and not within the normal tissue of the same patients. Our research aims to exploit the downregulation of this DNA repair gene by knocking down additional DNA repair proteins and look for synthetic lethality when treated with various chemotherapeutic drugs.