Telomeres consist of repetitive tracts of DNA that shield a chromosome’s contents from erosion and replicative attrition. However, telomeres are also late-replicating regions of the genome in which a myriad of replicative obstructions reside. The obstacles contained within telomeres, as well as their genomic location, drive replicative stalling and subsequent fork collapse in these regions. Consequently, large scale deletions, under-replicated DNA, translocations, and fusion events arise following telomere replication failure. Further, under-replicated DNA and telomere fusions that are permitted to enter mitosis will produce mitotic DNA bridges — known drivers of genetic loss and chromothripsis. Thus, aberrant telomere replication promotes genomic instability, which, in turn leads either to cellular death, senescence or oncogenic transformation. The importance of these issues for organismal well-being necessitates a need for resolute telomere maintenance. Here, we describe recent advances in identifying and understanding the molecular mechanisms that are in place in human cells to escort the replisome through the telomere’s unwieldy structures and repetitive sequences. Finally, we review the pathways that combat the deleterious outcomes that occur when telomeric replication forks do collapse.

端粒由DNA的重复片段组成，这些片段可保护染色体的内容免受侵蚀和复制损耗。但是，端粒也是基因组的后期复制区域，其中存在大量复制障碍。端粒中包含的障碍物及其基因组位置会导致复制失速和随后的叉子塌陷。因此，端粒复制失败后会出现大规模缺失，DNA复制不足，易位和融合事件。此外，被允许进入有丝分裂的复制不足的DNA和端粒融合体将产生有丝分裂DNA桥-已知的遗传损失和色杆菌病的驱动器。因此，端粒的异常复制会促进基因组的不稳定性，进而导致细胞死亡，衰老或致癌性转化。这些问题对于机体健康至关重要，因此需要坚决维护端粒。在这里，我们描述了鉴定和了解人类细胞中通过端粒的笨拙结构和重复序列护送复制体的分子机制的最新进展。最后，我们回顾了与端粒复制叉确实塌陷时所产生的有害结果作斗争的途径。