Utz Herbig, Ph.D.
With the exception of stem cells and cells from the germ line, all human somatic cells have a limited proliferative lifespan and eventually will become senescent. Similar to apoptosis, cellular senescence has been demonstrated to function as a potent tumor suppressor mechanism, preventing the accumulation of cells that encountered signaling imbalances and other transforming events. However, as senescent cells accumulate in living organisms, they potentially contribute to organismal aging by reducing the number of functional cells in various organ systems. Although cellular senescence will likely protect us from neoplasia, it might also reduce our lifespan by contributing to biological aging of multicellular organisms.
Our laboratory is interested in understanding how telomeres, the physical ends of linear chromosomes, contribute to senescence in mammalian cells. Telomeres consist of highly repetitive TTAGGG repeats that are associated with a large number of telomere-sequence specific and non-specicfic binding proteins. The function of telomeres is to protect the chromosome ends from nucleolytic degradation and DNA repair events in addition to serving as a buffer zone shielding genes positioned close to chromosome ends. Since linear chromosomes progressively shorten with every cell division, due to the inability of the replicative polymerase to completely duplicate linear DNA, these telomeric buffer zones therefore are critical to prevent the erosion and destruction of DNA sequences adjacent to telomeres. However, once telomeric DNA has eroded to a certain degree, telomeric structures fall apart and trigger a DNA damage response that ultimately results in growth arrest and senescence. Precisely how telomeres shorten, disassemble, and trigger senescence is currently under investigation in our lab. In addition, we are studying whether telomere induced senescence contributes to tumor suppression and organismal aging in mammals.
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