Spo11 generates gaps through concerted cuts at sites of topological stress
| Autor: | Doris Chen, Elisa Mayrhofer, Lingzhi Huang, Magdalena Vesely, Soma Zsótér, Jean Mbogning, Silvia Prieler, Franz Klein |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Multidisciplinary Spo11 biology Chemistry Base pair fungi Topology Chromosome segregation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Meiosis biology.protein Gene conversion Homologous recombination 030217 neurology & neurosurgery DNA 030304 developmental biology Heteroduplex |
| Zdroj: | Nature. 594:577-582 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Meiotic recombination is essential for chromosome segregation at meiosis and fertility. It is initiated by programmed DNA double-strand breaks (DSBs) introduced by Spo11, a eukaryotic homologue of an archaeal topoisomerase (Topo VIA)1. Here we describe previously uncharacterized Spo11-induced lesions, 34 to several hundred base pair-long gaps, which are generated by coordinated pairs of DSBs termed double DSBs. Isolation and genome-wide mapping of the resulting fragments with single base-pair precision revealed enrichment at DSB hotspots but also a widely dispersed distribution across the genome. Spo11 prefers to cut sequences with similarity to a DNA-bending motif2, which indicates that bendability contributes to the choice of cleavage site. Moreover, fragment lengths have a periodicity of approximately (10.4n + 3) base pairs, which indicates that Spo11 favours cleavage on the same face of underwound DNA. Consistently, double DSB signals overlap and correlate with topoisomerase II-binding sites, which points to a role for topological stress and DNA crossings in break formation, and suggests a model for the formation of DSBs and double DSBs in which Spo11 traps two DNA strands. Double DSB gaps, which make up an estimated 20% of all initiation events, can account for full gene conversion events that are independent of both Msh2-dependent heteroduplex repair3,4 and the MutLγ endonuclease4. Because non-homologous gap repair results in deletions, and ectopically re-integrated double DSB fragments result in insertions, the formation of double DSBs is a potential source of evolutionary diversity and pathogenic germline aberrations. Meiotic recombination in yeast is not only initiated by single break sites, but also caused by closely spaced Spo11-dependent double-stranded DNA breaks that create chromosomal gaps. |
| Databáze: | OpenAIRE |
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