ArticlePLoS biology2019
Repair of multiple simultaneous double-strand breaks causes bursts of genome-wide clustered hypermutation.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- Decoupling metabolic defense: Mutational and recombinational chaos in Sod1-deficient cells.PLoS genetics · 2026Article
- Article
- Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.NAR cancer · 2026Article
- Break-induced replication forms long mutable single-strand DNA during meiosis.Nature communications · 2026Article
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.G3 (Bethesda, Md.) · 2026Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide screen reveals dependence of break induced replication on several distinct checkpoints.Nature communications · 2025Article
- Mechanisms and genomic implications of break-induced replication.Nature structural & molecular biology · 2025Review
- Catalytically inactive Cas9 attenuates DNA end resection: A potential application for region-restricted random mutagenesis.iScience · 2025Article
- APOBEC affects tumor evolution and age at onset of lung cancer in smokers.Nature communications · 2025Article
- Hypomorphic mutation in the large subunit of replication protein A affects mutagenesis by human APOBEC cytidine deaminases in yeast.G3 (Bethesda, Md.) · 2024Article
- Stressed? Break-induced replication comes to the rescue!DNA repair · 2024Review
- Hypomorphic mutation in the large subunit of replication protein A affects mutagenesis by human APOBEC cytidine deaminases in yeast.bioRxiv : the preprint server for biology · 2024Article
- Monitoring Genomic Structural Rearrangements Resulting from Gene Editing.Journal of personalized medicine · 2024Article
- Generation and Repair of Postreplication Gaps in Escherichia coli.Microbiology and molecular biology reviews : MMBR · 2023Review
- Widely spaced and divergent inverted repeats become a potent source of chromosomal rearrangements in long single-stranded DNA regions.Nucleic acids research · 2023Article
- Influence network model uncovers relations between biological processes and mutational signatures.Genome medicine · 2023Article
- Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells.Scientific reports · 2022Article
- Competition for DNA binding between the genome protector replication protein A and the genome modifying APOBEC3 single-stranded DNA deaminases.Nucleic acids research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A single cancer genome can harbor thousands of clustered mutations. Mutation signature analyses have revealed that the origin of clusters are lesions in long tracts of single-stranded (ss) DNA damaged by apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases, raising questions about molecular mechanisms that generate long ssDNA vulnerable to hypermutation. Here, we show that ssDNA intermediates formed during the repair of gamma-induced bursts of double-strand breaks (DSBs) in the presence of APOBEC3A in yeast lead to multiple APOBEC-induced clusters similar to cancer. We identified three independent pathways enabling cluster formation associated with repairing bursts of DSBs: 5' to 3' bidirectional resection, unidirectional resection, and break-induced replication (BIR). Analysis of millions of mutations in APOBEC-hypermutated cancer genomes revealed that cancer tolerance to formation of hypermutable ssDNA is similar to yeast and that the predominant pattern of clustered mutagenesis is the same as in resection-defective yeast, suggesting that cluster formation in cancers is driven by a BIR-like mechanism. The phenomenon of genome-wide burst of clustered mutagenesis revealed by our study can play an important role in generating somatic hypermutation in cancers as well as in noncancerous cells.
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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.