DNA Repair at Telomeres: Keeping the Ends Intact

Abstract

The molecular era of telomere biology began with the discovery that telomeres usually consist of G-rich simple repeats and end with 3′ single-stranded tails. Enormous progress has been made in identifying the mechanisms that maintain and replenish telomeric DNA and the proteins that protect them from degradation, fusions, and checkpoint activation. Although telomeres in different organisms (or even in the same organism under different conditions) are maintained by different mechanisms, the disparate processes have the common goals of repairing defects caused by semiconservative replication through G-rich DNA, countering the shortening caused by incomplete replication, and postreplication regeneration of G tails. In addition, standard DNA repair mechanisms must be suppressed or modified at telomeres to prevent their being recognized and processed as DNA double-strand breaks. Here, we discuss the players and processes that maintain and regenerate telomere structure.

Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding

“…In addition, 59.4% of wild-type repeats lacked a (G) [1][2][3][4][5][6] tract. Thus, the chance of four tandem repeats without a (G) [1][2][3][4][5][6] tract is 12.4%, which leads to a probability of only 0.0009% for (5′-GGTTACAC-3′) 4 in wild-type telomeric DNA. We conclude that the frequency of (5′-GGTTACAC-3′) 4 in 759 ter1-STE loop telomeric repeats (Fig.…”

“…Almost half (42%) of the telomeric repeats are preceded by a guanine tract of 1-6 Gs, whereas the rare cytosine is present in ∼12% of the repeats (5). The (G) [1][2][3][4][5][6] tracts result from template stuttering between the 3′ end of the telomerase RNA template and the end of the telomere (Fig. S1, Left).…”

“…The shelterin complex binds both double-stranded (ds) telomeric DNA and the terminal single-stranded (ss) guanine-rich overhang, known as the G-tail (3). The ds region of S. pombe telomeres is bound by the Myb domain of the S. pombe shelterin component Taz1 (telomere-associated in Schizosaccharomyces pombe 1), whereas the G-tail is bound by the OB domains of Pot1 (protection of telomeres 1).…”

“…The ds region of S. pombe telomeres is bound by the Myb domain of the S. pombe shelterin component Taz1 (telomere-associated in Schizosaccharomyces pombe 1), whereas the G-tail is bound by the OB domains of Pot1 (protection of telomeres 1). Both the Myb and OB (oligonucleotide/oligosaccharidebinding) domains are present in the mammalian homologs of these proteins, TRF1/TRF2 and POT1, respectively (1)(2)(3).…”

“…In the fission yeast Schizosaccharomyces pombe, telomeric DNA is bound and protected by a six-protein complex that has many similarities to mammalian shelterin. S. pombe shelterin protects the telomere, inhibits nonhomologous end joining, facilitates telomere replication, and recruits telomerase (1)(2)(3).…”