Telomere Fragility and MiDAS: Managing the Gaps at the End of the Road

Telomeres present inherent difficulties to the DNA replication machinery due to their repetitive sequence content, formation of non-B DNA secondary structures, and the presence of the nucleo-protein t-loop. Especially in cancer cells, telomeres are hot spots for replication stress, which can result in a visible phenotype in metaphase cells termed telomere fragility. A mechanism cells employ to mitigate replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). While these phenomena are both observed in mitotic cells, the relationship between them is poorly understood; however, a common link is DNA replication stress. In this review, we will summarize what is known to regulate telomere fragility and telomere MiDAS, paying special attention to the proteins which play a role in these telomere phenotypes.

Automated summary

Telomeres present challenges for DNA replication due to their repetitive sequences, non-B DNA structures, and the presence of nucleo-protein t-loops. Telomeres are particularly susceptible to replication stress in cancer cells, resulting in telomere fragility in metaphase cells. One mechanism cells use to cope with replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). Although both phenomena are observed in mitotic cells, the relationship between them is poorly understood, but they are both linked by DNA replication stress. In this review, we summarize the regulation of telomere fragility and telomere MiDAS, focusing on the proteins involved in these telomere phenotypes.