Actin and myosin in genome stability and integrity in response to DNA damage

Bakgrund

One of the most fascinating goals of molecular genetics is to study the architecture of the genome and how this influences expression of genes required for cellular functions. This process is critical for the survival and maintenance of all individual species. In healthy individuals, upon DNA damage, gene expression is halted in order to repair the DNA. However, in cancer the repair mechanisms do not work properly, we have loss of genomic stability and integrity, resulting in excessive cell growth and proliferation. Thus, understanding genome organization, stability and integrity becomes one of the priorities in the broad area of “health”.

Beskrivning

A fundamental question is how the architecture of the genome and its integrity ensure sustained expression of genes. We work on the hypothesis that cytoskeletal proteins such as actin and myosin play an important role in genome organization and recent evidence indicates that they are necessary in response to DNA damage, although the mechanisms are not fully understood. In this proposal we focus on a form of myosin 1 that appears to play an important role as gatekeeper of genome stability and integrity and it is believed to function as tumor suppressor by regulating p53 signaling, a hallmark for aggressive tumors.

Mål

While this proposal may provide important mechanistic insights into how the cell responds to DNA damage factors in order to maintain genome integrity, in the long-term results from these studies may identify novel factors and pathways to be targeted for clinical applications in aggressive tumors.