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...

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Bibliographic Details
Published in:Genes 2023-01, Vol.14 (2), p.348
Main Authors: Barnes, Ryan P, Thosar, Sanjana A, Opresko, Patricia L
Format: Article
Language:English
Subjects:
Cancer
Deoxyribonucleic acid
DNA
DNA - metabolism
DNA biosynthesis
DNA polymerase
DNA Replication
DNA synthesis
Genetic aspects
Genotype & phenotype
Kinases
Metaphase
Mitosis
Mutation
Nucleotide sequence
Phenotype
Phenotypes
Physiological aspects
Replication
Review
Telomerase
Telomere - metabolism
Telomeres
Yeast
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Summary: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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14020348