Eric A. Hendrickson, PhD, a professor in the Department of Medicine, Division of Hematology and Oncology and an affiliate member of the Department of Biochemistry and Molecular Genetics, was awarded a 5-year, $2.3 million grant from the NCI to study how the alternative non-homologous end joining (A-NHEJ) pathway regulates telomere fusions during crisis.
Aging human cells undergo a reproducible erosion of the ends of their chromosomes (structures termed telomeres) that signal the cell to stop proliferating and to enter a senescent-like state. Cells that do not arrest when they should continue to suffer telomere erosion until they enter a second state termed “crisis.” During crisis, massive genomic instability, triggered by the ultra-short telomeres, results in a plethora of chromosomal fusions and aberrations that cause the death of 99.9% of the cells. Alas, rare survivors can arise termed “immortalized” and immortalized cells will now proliferate indefinitely until they give rise to a cancer. Dr. Hendrickson and his team have demonstrated that the A-NHEJ pathway, in particular a gene called POLQ, is absolutely required for immortalization to occur in human somatic cells. The fact that a veritable bevy of pharmaceutical companies have sprung up around the concept of inhibiting POLQ lends strong support to the idea that inhibition of POLQ (and hence inhibition of immortalization), is a highly promising clinical therapeutic strategy.
Duncan Baird, PhD, in the Division of Cancer and Genetics, School of Medicine at Cardiff University, Wales UK, is a collaborator on this award.