Telomeres shorten during each cellular division, with cumulative attrition resulting in telomeric damage and replicative senescence. Bypass of replicative senescence precipitates catastrophic telomere shortening or crisis, and is characterized by widespread genomic instability. Activation of a telomere maintenance mechanism (TMM) is necessary to stabilise the genome and establish cellular immortality through the reconstitution of telomere capping function. The alternative lengthening of telomeres (ALT) pathway is a TMM frequently activated in tumors of mesenchymal or neuroepithelial origin. ALT is a homology-directed recombination-dependent replication pathway that utilizes telomeric templates for synthesis; however, its precise protein requirements have remained elusive. Recently, several developments have shed light on the DNA repair pathways that become engaged at ALT telomeres, implicating ALT telomeres as DNA repair hot spots. Here, we review recent discoveries regarding the ALT mechanism, and discuss how DNA repair pathways converge to maintain the length and functional integrity of telomeres in ALT cancers.

端粒在每个细胞分裂过程中都会缩短，累积的磨损会导致端粒损伤和复制性衰老。复制性衰老的绕过导致灾难性的端粒缩短或危机，并且以广泛的基因组不稳定性为特征。端粒维持机制（TMM）的激活对于稳定基因组和通过端粒加帽功能的重建建立细胞永生是必要的。端粒（ALT）通路的替代性延长是TMM，通常在间充质或神经上皮起源的肿瘤中被激活。ALT是一种同源性指导的重组依赖性复制途径，该途径利用端粒模板进行合成。然而，其精确的蛋白质需求仍然难以捉摸。最近，几个发展趋势揭示了参与ALT端粒的DNA修复途径，暗示ALT端粒是DNA修复的热点。在这里，我们回顾有关ALT机制的最新发现，并讨论DNA修复途径如何收敛以维持ALT癌中端粒的长度和功能完整性。