To maintain genome stability, cells must promptly detect and repair DNA lesions, particularly DNA double-strand breaks (DSBs). Unrepaired DSBs can lead to chromosome loss, while errors in repair result in mutations and genome rearrangements.
At the same time, eukaryotic cells must protect their chromosome ends, called telomeres, from being mistakenly recognized and aberrantly repaired as DNA damage. Although telomere shortening acts as a natural barrier to uncontrolled cell proliferation, defects in telomere protection are associated with tumorigenesis, cellular senescence, and rare human diseases known as telomeropathies.
Importantly, several cancer therapies exploit this vulnerability by inducing genome instability beyond repair, thereby triggering cell death in targeted cancer cells. To investigate these processes in normal and cancer cells, we combine mouse and human cell genetics with advanced imaging techniques—including live-cell imaging and electron microscopy—to analyze genome stability at the molecular level. Our main areas of study focus on the role of nuclear structure in DSB mobility and (mis)repair and the regulation of DSB repair pathways activation and inhibition at telomeres.
