Journal article
Break-induced replication forms long mutable single-strand DNA during meiosis
Nature communications
06/20/2026
DOI: 10.1038/s41467-026-74270-y
PMID: 42323311
Abstract
In meiosis, homologous recombination (HR) facilitates the halving of genomic content in diploid parents to produce haploid gametes, while also reshuffling genetic material. However, studies in yeast and mammals have suggested that HR during meiosis also makes the process mutagenic, and it has been proposed that the single-strand (ss) DNA formed by HR of programmed double-strand breaks (DSBs) contributes to the observed mutagenesis. To determine the full mutagenic potential of ssDNA formed during meiosis, we expressed human APOBEC3A (A3A), a deaminase that specifically attacks and therefore allows detection of ssDNA, in meiotic yeast cells. We demonstrate that meiotic cells accumulate long tracts of ssDNA manifested by A3A-mutation clusters, of up to 134 mutations spanning more than 25 kb. We show that the formation of mutation clusters during meiosis require Spo11-induced DSBs, and that break-induced replication and hyper-resection of DSBs are the primary mechanisms underlying the formation of long ssDNA. We also report meiotic ssDNA accumulation in promoters and tRNA genes, revealing them as additional sources of mutagenesis during meiosis. Together, our results demonstrate the high mutagenic potential of meiosis and provide insight into mechanisms that can fuel evolution and promote congenital diseases in humans.
Details
- Title: Subtitle
- Break-induced replication forms long mutable single-strand DNA during meiosis
- Creators
- Jerzy M Twarowski - University of IowaJuraj Kramara - University of IowaGabriel J Seuferer - The University of Texas at San Antonio Health Science CenterKelley A Renninger - The University of Texas at San Antonio Health Science CenterJosep M Comeron - University of IowaAnna Malkova - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature communications
- DOI
- 10.1038/s41467-026-74270-y
- PMID
- 42323311
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Nature
- Grant note
- R35GM127006 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) RR240030 / Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
- Language
- English
- Electronic publication date
- 06/20/2026
- Academic Unit
- Stead Family Department of Pediatrics; Biology; Infectious Disease (Pediatrics)
- Record Identifier
- 9985176652902771
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