Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells

摘要: In normal cells, telomeres shorten each time a cell divides ultimately resulting in senescence. contrast, cancer cells counteract the loss of telomeric DNA either by inducing expression telomerase or activating alternative lengthening (ALT) pathway. ALT are characterized heterogeneous and presence extrachromosomal circular double-stranded molecules containing repeat sequences. These circles (t-circles) though to be generated through recombination process utilized as templates for telomere elongation rolling-circle-replication, although their precise mechanism formation role maintenance proliferation is largely unknown. Here we show that shRNA-mediated knockdown Ku70/80 heterodimer, factor with functions at both pathological natural ends, inhibits growth results significant decrease levels t-circles without affecting overall length. findings demonstrate non homology-based processes contribute cells.