ArticleGenes & development2018
Repeat-mediated deletions can be induced by a chromosomal break far from a repeat, but multiple pathways suppress such rearrangements.
Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 51 citations in OpenAlex.
- LINE-1 insertion intermediates recombine with one another or with DNA breaks to form genome rearrangements.Nature communications · 2026Article
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Microhomology-mediated end joining is the predominant form of DNA repair in the mosquito Aedes aegypti with implications for gene editing, gene drive, and transgene removal.Nucleic acids research · 2026Article
- L1 insertion intermediates recombine with one another or with DNA breaks to form genome rearrangements.bioRxiv : the preprint server for biology · 2025Article
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.bioRxiv : the preprint server for biology · 2025Article
- DNA nicks in both leading and lagging strand templates can trigger break-induced replication.Molecular cell · 2025Article
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.DNA repair · 2025Article
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.Translational medicine of aging · 2025Article
- The Role of Endoplasmic Reticulum Stress on Reducing Recombinant Protein Production in Mammalian Cells.Biochemical engineering journal · 2024Article
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.bioRxiv : the preprint server for biology · 2024Article
- Transgene removal using an in cis programmed homing endonuclease via single-strand annealing in the mosquito Aedes aegypti.Communications biology · 2024Article
- Nonhomologous tails direct heteroduplex rejection and mismatch correction during single-strand annealing in Saccharomyces cerevisiae.PLoS genetics · 2024Article
- LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities.Genes & development · 2023Review
- Enhancement of Repeat-Mediated Deletion Rearrangement Induced by Particle Irradiation in aBiology · 2023Article
- Targeting the DNA Damage Response for Cancer Therapy.International journal of molecular sciences · 2023Review
- Exome sequencing identified rare recurrent copy number variants and hereditary breast cancer susceptibility.PLoS genetics · 2023Article
- DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy.Cancers · 2023Review
- Resolution of sequence divergence for repeat-mediated deletions shows a polarity that is mediated by MLH1.Nucleic acids research · 2023Article
- The effect of repeat length on Marcal1-dependent single-strand annealing in Drosophila.Genetics · 2023Article
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3 authors at 2 institutions in 1 country.
Funding
Abstract
Chromosomal deletion rearrangements mediated by repetitive elements often involve repeats separated by several kilobases and sequences that are divergent. While such rearrangements are likely induced by DNA double-strand breaks (DSBs), it has been unclear how the proximity of DSBs relative to repeat sequences affects the frequency of such events. We generated a reporter assay in mouse cells for a deletion rearrangement involving repeats separated by 0.4 Mb. We induced this repeat-mediated deletion (RMD) rearrangement with two DSBs: the 5' DSB that is just downstream from the first repeat and the 3' DSB that is varying distances upstream of the second repeat. Strikingly, we found that increasing the 3' DSB/repeat distance from 3.3 kb to 28.4 kb causes only a modest decrease in rearrangement frequency. We also found that RMDs are suppressed by KU70 and RAD51 and promoted by RAD52, CtIP, and BRCA1. In addition, we found that 1%-3% sequence divergence substantially suppresses these rearrangements in a manner dependent on the mismatch repair factor MSH2, which is dominant over the suppressive role of KU70. We suggest that a DSB far from a repeat can stimulate repeat-mediated rearrangements, but multiple pathways suppress these events.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.