Alternative lengthening of telomeres in mammalian cells

摘要: Some immortalized mammalian cell lines and tumors maintain or increase the overall length of their telomeres in absence telomerase activity by one more mechanisms referred to as alternative lengthening (ALT). Characteristics human ALT cells include great heterogeneity telomere size (ranging from undetectable abnormally long) within individual cells, ALT-associated PML bodies (APBs) that contain extrachromosomal telomeric DNA, telomere-specific binding proteins, proteins involved DNA recombination replication. Activation during immortalization involves recessive mutations genes are yet unidentified. Repressors present normal some telomerase-positive cells. Telomere dynamics suggest a recombinational mechanism. Inter-telomeric copying occurs, consistent with mechanism which single-stranded at terminus invades another uses it copy template resulting net sequence. It is possible t-loops, linear and/or circular found APBs, may be can co-exist cultured tumors. The existence adds complexity proposed telomere-related parameters cancer diagnosis prognosis, poses challenges for design anticancer therapeutics designed inhibit maintenance.