Abstract
Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB) induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage.
Highlights
Telomeres are specialized nucleoprotein complexes at the ends of linear eukaryotic chromosomes
In this paper we provide evidence suggesting an alternative Rap1-dependent telomere shortening mechanism in which binding of multiple Rap1 proteins mediates DNA break induction during DNA replication
We examined whether Rap1 is involved in double-stranded break (DSB) induction, thereby converting internal tracts of TG sequence to telomeres
Summary
Telomeres are specialized nucleoprotein complexes at the ends of linear eukaryotic chromosomes. The DNA component of telomeres typically comprises a double-stranded DNA (dsDNA) region of a tandem repeat and a 3’ protruding single-stranded DNA (ssDNA) region of the G-rich strand [1,2]. Both the dsDNA and ssDNA regions are covered with sequence-specific binding proteins. Telomeres protect chromosome ends from degradation or fusion [2,3]. Telomeres promote DNA replication at the chromosome ends. Since conventional DNA polymerases cannot complete DNA synthesis at telomeres, linear chromosomes shorten progressively with every round of cell division. Continuous telomere shortening can be counteracted by telomerase [4]
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