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Updated: Feb 9, 2026
Generation of Cancer Cell Clones to Visualize Telomeric Repeat-containing RNA TERRA Expressed from a Single Telomere in Living Cells
Published on: January 17, 2019
Chromosome fusions following telomere loss are mediated by single-strand annealing
Xiaorong Wang1, Peter Baumann2
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Abstract:
Progressive telomere shortening eventually results in chromosome fusions and genome instability as the cell's ability to distinguish chromosome ends from DNA double-strand breaks is compromised. In fission yeast, such events frequently produce stable survivors with all circular chromosomes. To shed light on the repair pathways that mediate chromosome end fusions and generate circular chromosomes, we have examined a diverse array of DNA repair factors. We show that telomere attrition-induced chromosome fusions are dependent on the fission yeast homologs of Rad52, the ERCC1/XPF endonuclease, the single-stranded DNA-binding protein RPA, and the Srs2 and Werner/Bloom helicases, but not Ku and ligase 4. Consistent with a recombinational mechanism of single-strand annealing, cloned junctions map to four of five homology regions in subtelomeric DNA. A comparison with telomere uncapping caused by the absence of the double-stranded telomere-binding protein Taz1 demonstrates that the circumstances and cause of telomere dysfunction profoundly affect which DNA repair pathway is engaged.
Insights
Telomere shortening causes chromosome fusions in fission yeast. Specific DNA repair factors, including Rad52 homologs and helicases, mediate these fusions and circular chromosome formation, revealing key genome stability mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Progressive telomere shortening leads to genome instability and chromosome fusions.
- In fission yeast, telomere attrition can result in stable, circularized chromosomes.
Purpose of the Study:
- To investigate the DNA repair pathways involved in telomere end fusions.
- To understand the mechanisms generating circular chromosomes after telomere dysfunction.
Main Methods:
- Examined the roles of various DNA repair factors in fission yeast.
- Analyzed chromosome fusions and junctions resulting from telomere attrition.
- Compared repair pathways activated by telomere shortening versus telomere uncapping.
Main Results:
- Chromosome fusions due to telomere attrition depend on Rad52 homologs, ERCC1/XPF endonuclease, RPA, Srs2, and Werner/Bloom helicases.
- These fusions are independent of Ku and ligase 4.
- Cloned junctions indicate a single-strand annealing mechanism involving subtelomeric homology regions.
- The cause of telomere dysfunction influences the engaged DNA repair pathway.
Conclusions:
- Recombinational repair pathways, particularly single-strand annealing, are critical for resolving telomere fusions and forming circular chromosomes in fission yeast.
- The cellular response to telomere dysfunction is context-dependent, highlighting the plasticity of genome maintenance mechanisms.
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