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DNA Replication Origins and Fork Progression at Mammalian Telomeres

Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Authors to whom correspondence should be addressed.
Academic Editor: Eishi Noguchi
Genes 2017, 8(4), 112;
Received: 7 February 2017 / Revised: 23 March 2017 / Accepted: 24 March 2017 / Published: 28 March 2017
(This article belongs to the Special Issue DNA Replication Controls)
PDF [841 KB, uploaded 30 March 2017]


Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions. View Full-Text
Keywords: DNA replication; genome integrity; telomere; shelterin; G-quadruplex; RecQ-like helicase; fragile telomere; replication fork barrier; dormant origin DNA replication; genome integrity; telomere; shelterin; G-quadruplex; RecQ-like helicase; fragile telomere; replication fork barrier; dormant origin

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Higa, M.; Fujita, M.; Yoshida, K. DNA Replication Origins and Fork Progression at Mammalian Telomeres. Genes 2017, 8, 112.

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