Gradual implementation of the meiotic recombination program via checkpoint pathways controlled by global DSB levels.
Mol Cell
; 57(5): 797-811, 2015 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-25661491
ABSTRACT
During meiosis, Spo11-induced double-strand breaks (DSBs) are processed into crossovers, ensuring segregation of homologous chromosomes (homologs). Meiotic DSB processing entails 5' end resection and preferred strand exchange with the homolog rather than the sister chromatid (homolog bias). In many organisms, DSBs appear gradually along the genome. Here we report unexpected effects of global DSB levels on local recombination events. Early-occurring, low-abundance "scout" DSBs lack homolog bias. Their resection and interhomolog processing are controlled by the conserved checkpoint proteins Tel1(ATM) kinase and Pch2(TRIP13) ATPase. Processing pathways controlled by Mec1(ATR) kinase take over these functions only above a distinct DSB threshold, resulting in progressive strengthening of the homolog bias. We conclude that Tel1(ATM)/Pch2 and Mec1(ATR) DNA damage response pathways are sequentially activated during wild-type meiosis because of their distinct sensitivities to global DSB levels. Moreover, relative DSB order controls the DSB repair pathway choice and, ultimately, recombination outcome.
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Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Transducción de Señal
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Roturas del ADN de Doble Cadena
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Recombinación Homóloga
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Meiosis
Tipo de estudio:
Prognostic_studies
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Sysrev_observational_studies
Idioma:
En
Año:
2015
Tipo del documento:
Article