
pmid: 25329304
pmc: PMC4199488
Broken replication forks result in DNA breaks that are normally repaired via homologous recombination or break induced replication (BIR). Mild insufficiency in the replicative ligase Cdc9 in budding yeast Saccharomyces cerevisiae resulted in a population of cells with persistent DNA damage, most likely due to broken replication forks, constitutive activation of the DNA damage checkpoint and longer telomeres. This telomere lengthening required functional telomerase, the core DNA damage signaling cascade Mec1-Rad9-Rad53, and the components of the BIR repair pathway - Rad51, Rad52, Pol32, and Pif1. The Mec1-Rad53 induced phosphorylation of Pif1, previously found necessary for inhibition of telomerase at double strand breaks, was also important for the role of Pif1 in BIR and telomere elongation in cdc9-1 cells. Two other mutants with impaired DNA replication, cdc44-5 and rrm3Δ, were similar to cdc9-1: their long telomere phenotype was dependent on the Pif1 phosphorylation locus. We propose a model whereby the passage of BIR forks through telomeres promotes telomerase activity and leads to telomere lengthening.
DNA Replication, Saccharomyces cerevisiae Proteins, DNA Ligases, DNA Helicases, Intracellular Signaling Peptides and Proteins, Telomere Homeostasis, Cell Cycle Proteins, QH426-470, Protein Serine-Threonine Kinases, Checkpoint Kinase 2, DNA Ligase ATP, Mutation, Genetics, DNA Breaks, Single-Stranded, Phosphorylation, Replication Protein C, Telomerase, Research Article, DNA Damage, Signal Transduction
DNA Replication, Saccharomyces cerevisiae Proteins, DNA Ligases, DNA Helicases, Intracellular Signaling Peptides and Proteins, Telomere Homeostasis, Cell Cycle Proteins, QH426-470, Protein Serine-Threonine Kinases, Checkpoint Kinase 2, DNA Ligase ATP, Mutation, Genetics, DNA Breaks, Single-Stranded, Phosphorylation, Replication Protein C, Telomerase, Research Article, DNA Damage, Signal Transduction
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