Conserved Telomere Maintenance Component 1 Interacts with STN1 and Maintains Chromosome Ends in Higher Eukaryotes

Recombination, Genetic 0303 health sciences Arabidopsis Proteins Chromosomal Proteins, Non-Histone Telomere-Binding Proteins Arabidopsis Cell Biology Telomere Chromosomes, Plant Genomic Instability 03 medical and health sciences Eukaryotic Cells Cell Line, Tumor Mutation Humans Nucleic Acid Conformation Anaphase Molecular Biology Conserved Sequence In Situ Hybridization, Fluorescence Protein Binding
DOI: 10.1016/j.molcel.2009.09.017 Publication Date: 2009-10-23T09:15:31Z
ABSTRACT
Orthologs of the yeast telomere protein Stn1 are present in plants, but other components of the Cdc13/Stn1/Ten1 (CST) complex have only been found in fungi. Here we report the identification of conserved telomere maintenance component 1 (CTC1) in plants and vertebrates. CTC1 encodes an approximately 140 kDa telomere-associated protein predicted to contain multiple OB-fold domains. Arabidopsis mutants null for CTC1 display a severe telomere deprotection phenotype accompanied by a rapid onset of developmental defects and sterility. Telomeric and subtelomeric tracts are dramatically eroded, and chromosome ends exhibit increased G overhangs, recombination, and end-to-end fusions. AtCTC1 both physically and genetically interacts with AtSTN1. Depletion of human CTC1 by RNAi triggers a DNA damage response, chromatin bridges, increased G overhangs, and sporadic telomere loss. These data indicate that CTC1 participates in telomere maintenance in diverse species and that a CST-like complex is required for telomere integrity in multicellular organisms.
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