ArticleNucleic acids research2023
Widely spaced and divergent inverted repeats become a potent source of chromosomal rearrangements in long single-stranded DNA regions.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- RoCi-a single-step multi-copy integration system based on rolling-circle replication.Nucleic acids research · 2026Article
- A breakage-replication/fusion process explains complex rearrangements and segmental DNA amplification.Nature genetics · 2026Article
- Overcoming natural replication barriers formed by DNA structures and the role of repositioning to the nuclear periphery.DNA repair · 2025Review
- High-Resolution Assembly of the Human Y Chromosome Identifies a Vast Landscape of Inverted Repeats Associated with Structural and Functional Genomic Features.International journal of molecular sciences · 2025Article
- Assessment and Mitigation of CRISPR-Cas9-Induced Nontargeted Translocations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DNA polymerase zeta can efficiently replicate structures formed by AT/TA repeat sequences and prevent their deletion.Nucleic acids research · 2025Article
- Combining long-read DNA and RNA sequencing to enhance molecular understanding of structural variations leading to copy gains.Computational and structural biotechnology journal · 2025Article
- POLD3 as Controller of Replicative DNA Repair.International journal of molecular sciences · 2024Review
- How to sensitize glioblastomas to temozolomide chemotherapy: a gap-centered view.Frontiers in cell and developmental biology · 2024Review
- Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism.Nature communications · 2023Article
- Unveiling the toxicity of single-stranded DNA gaps through a yeast model.Nature structural & molecular biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
DNA inverted repeats (IRs) are widespread across many eukaryotic genomes. Their ability to form stable hairpin/cruciform secondary structures is causative in triggering chromosome instability leading to several human diseases. Distance and sequence divergence between IRs are inversely correlated with their ability to induce gross chromosomal rearrangements (GCRs) because of a lesser probability of secondary structure formation and chromosomal breakage. In this study, we demonstrate that structural parameters that normally constrain the instability of IRs are overcome when the repeats interact in single-stranded DNA (ssDNA). We established a system in budding yeast whereby >73 kb of ssDNA can be formed in cdc13-707fs mutants. We found that in ssDNA, 12 bp or 30 kb spaced Alu-IRs show similarly high levels of GCRs, while heterology only beyond 25% suppresses IR-induced instability. Mechanistically, rearrangements arise after cis-interaction of IRs leading to a DNA fold-back and the formation of a dicentric chromosome, which requires Rad52/Rad59 for IR annealing as well as Rad1-Rad10, Slx4, Msh2/Msh3 and Saw1 proteins for nonhomologous tail removal. Importantly, using structural characteristics rendering IRs permissive to DNA fold-back in yeast, we found that ssDNA regions mapped in cancer genomes contain a substantial number of potentially interacting and unstable IRs.
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Registered trials
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