The Configuration of RPA, RAD51, and DMC1 Binding in Meiosis Reveals the Nature of Critical Recombination Intermediates.
Mol Cell
; 79(4): 689-701.e10, 2020 08 20.
Article
em En
| MEDLINE
| ID: mdl-32610038
ABSTRACT
Meiotic recombination proceeds via binding of RPA, RAD51, and DMC1 to single-stranded DNA (ssDNA) substrates created after formation of programmed DNA double-strand breaks. Here we report high-resolution in vivo maps of RPA and RAD51 in meiosis, mapping their binding locations and lifespans to individual homologous chromosomes using a genetically engineered hybrid mouse. Together with high-resolution microscopy and DMC1 binding maps, we show that DMC1 and RAD51 have distinct spatial localization on ssDNA DMC1 binds near the break site, and RAD51 binds away from it. We characterize inter-homolog recombination intermediates bound by RPA in vivo, with properties expected for the critical displacement loop (D-loop) intermediates. These data support the hypothesis that DMC1, not RAD51, performs strand exchange in mammalian meiosis. RPA-bound D-loops can be resolved as crossovers or non-crossovers, but crossover-destined D-loops may have longer lifespans. D-loops resemble crossover gene conversions in size, but their extent is similar in both repair pathways.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
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Proteínas de Ligação a Fosfato
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Rad51 Recombinase
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Proteína de Replicação A
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Recombinação Homóloga
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Meiose
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article