TY - JOUR
T1 - DNA replication origins and fork progression at mammalian telomeres
AU - Higa, Mitsunori
AU - Fujita, Masatoshi
AU - Yoshida, Kazumasa
N1 - Funding Information:
We apologize to those whose work we were unable to cite due to space limitations. We thank members of the Fujita lab for helpful discussion and comments on the manuscript. This work was supported in part by Grants to Masatoshi Fujita and Kazumasa Yoshida from the Ministry of Education, Science, Sports, Technology and Culture of Japan.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
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U2 - 10.3390/genes8040112
DO - 10.3390/genes8040112
M3 - Review article
AN - SCOPUS:85016425887
VL - 8
JO - Genes
JF - Genes
SN - 2073-4425
IS - 4
M1 - 112
ER -