Checkpoint mechanisms that safeguard the mitochondrial genome and their role in cancer development
The genetic information in mitochondrial DNA is essential to us, and certain alterations to this information can cause cancer. The cell has mechanisms to protect the genetic information in its nuclear genome, but little is known about how the stability of the mitochondrial DNA is guaranteed.
This project will shed light on the mechanisms that detect or respond to problems in the mitochondrial genome, which on the long run can contribute to the development of better treatments.
The accumulation of mutations and rearrangements in our genome, collectively termed genome instability, plays a critical role in cancer initiation and progression. To protect our genome from instability, cells have developed a complex signalling network called the DNA damage response (the DNA damage checkpoints).
The importance of the DNA damage checkpoints is underscored by hereditary cancer predisposition syndromes caused by defects in these pathways. Recently, a novel checkpoint pathway called the mtDNA inheritance checkpoint that prevents the loss of our second genome, the mitochondrial DNA (mtDNA), has been discovered in budding yeast. Because intact mitochondrial function is essential to cancer cells, the newly-discovered mtDNA inheritance checkpoint that safeguards the mtDNA is highly relevant to cancer development.
However, very little is yet known about the role of the mtDNA inheritance checkpoint, and its components have not been identified. We aim to elucidate the function and components of the mtDNA checkpoint as well as their relevance during cancer development.
Fulfilling these aims will lead to a deeper understanding of the mtDNA checkpoint pathway and its role in cancer cells, which can inform future efforts to develop improved and personalized cancer treatment.