BMC Seminar - Role of ALKBH3 in the regulation of DNA DSB repair

BMC Seminar Thursday 4th of April at 12:00 in room 201 Læknagarður

Speaker: Dr. Þorkell Guðjónsson, senior scientis at Cancer Research Laboratory, Faculty of Medicine, Sturlugata 8, Reykjavik.

Title: The role of ALKBH3 in the regulation of DNA double strand break repair

Abstract: From the thousands of DNA lesions encountered daily by the human genome, DNA double strand breaks (DSBs) are considered to be the most cytotoxic. Unrepaired or incorrectly repaired DSB have the potential to alter the content and organization of the genome, which can have life-threatening consequences. ALKBH3 is a dioxygenase with a well-described function in DNA alkylation repair and RNA demethylation. In our previous work we showed clinically relevant epigenetic silencing of ALKBH3 in breast cancer suggesting potential tumor suppressive function.

In this presentation I will discuss findings that strongly suggest that in addition to its described function in DNA alkylation repair, ALKBH3 also plays an important role in the regulation of DNA DSB repair. Our hypothesis is that ALKBH3 is doing so by removing methylation marks of mRNA and subsequent translation of important DNA DSB proteins. Our data uncovers a novel function for ALKBH3 and a previously unrecognized crosstalk between two essential repair pathways, alkylation repair and DNA DSB repair. It also introduces mRNA modifications as a novel regulatory mechanism in DNA DSB repair signaling.