Genetic dissection of MutL complexes in <i>Arabidopsis</i> meiosis

During meiosis, homologous chromosomes exchange genetic material through crossing over. The main crossover pathway relies on ZMM proteins, including ZIP4 and HEI10, and is typically resolved by the MLH1/MLH3 heterodimer, MutLγ. Our analysis shows that while MUS81 may partially compensate for MutLγ l...

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Detalles Bibliográficos
Autores: Kbiri, Nadia, Fernández Jiménez, Nadia, Dziegielewski, Wojciech, Sáez-Zárate, Esperanza, Pelé, Alexandre, Mata-Villanueva, Ana, Dluzewska, Julia, Santos Coloma, Juan Luis, Pradillo Orellana, Mónica, Ziolkowski, Piotr A
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/120220
Acceso en línea:https://hdl.handle.net/20.500.14352/120220
Access Level:acceso abierto
Palabra clave:575.113.1
Genética
Biología molecular (Biología)
Fisiología vegetal (Biología)
Biología celular (Biología)
2409 Genética
2415 Biología Molecular
2407.02 Citogenética
2417.14 Genética Vegetal
Descripción
Sumario:During meiosis, homologous chromosomes exchange genetic material through crossing over. The main crossover pathway relies on ZMM proteins, including ZIP4 and HEI10, and is typically resolved by the MLH1/MLH3 heterodimer, MutLγ. Our analysis shows that while MUS81 may partially compensate for MutLγ loss, its role remains uncertain. However, our multiple mutant analysis shows that MUS81 is unlikely to be the sole resolvase of ZMM-protected recombination intermediates when MutLγ is absent. Comparing genome-wide crossover maps of mlh1 mutants with ZMM-deficient mutants and lines with varying HEI10 levels reveals that crossover interference persists in mlh1 but is weakened. The significant crossover reduction in mlh1 also increases aneuploidy in offspring. The loss of MutLγ can be suppressed by eliminating the FANCM helicase. Combined with the lower-than-expected chiasma frequency, this suggests that in MutLγ absence, some ZMM-protected intermediates are ultimately resolved by DNA helicases and/or their complexes with Top3α. Elevated MLH1 or MLH3 expression moderately increases crossover frequency, while their misregulation drastically reduces crossover numbers and plant fertility, highlighting the importance for tight control of MLH1/MLH3 levels. By contrast, PMS1, a component of the MutLα endonuclease, appears uninvolved in crossing over. Together, these findings demonstrate the unique role of MutLγ in ZMM-dependent crossover regulation.