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Frequency and Distribution of Crossovers in Caenorhabditis elegans Meiosis by SNP Genotyping using Real-time PCR
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La delineación de las vías de resolución de moléculas conjuntas en la meiosis identifica una resolvase específica de
Kseniya Zakharyevich1, Shangming Tang, Yunmei Ma
1Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Cell
|April 17, 2012
Resumen
Tres enzimas resuelven las uniones de Holliday durante la meiosis, pero una nueva vía que involucra a Sgs1, Exo1 y Mlh1-Mlh3 es crucial para la formación de cruces en levaduras y mamíferos.
Área de la Ciencia:
- Genética La genética.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La recombinación homóloga culmina en la resolución de la unión de Holliday (HJ), produciendo productos cruzados (CO) o no cruzados.
- Las enzimas específicas que gobiernan la resolución de la HJ in vivo han permanecido evasivas.
- Las tres resoluciones candidatas de la HJ identificadas in vitro incluyen Mus81-Mms4, Slx1-Slx4 y Yen1.1.
Objetivo del estudio:
- Investigar las funciones in vivo de Mus81-Mms4, Slx1-Slx4 y Yen1 en la resolución de la unión meiotica de Holliday.
- Identificar los factores y vías clave responsables de la formación de cruces durante la meiosis.
Principales métodos:
- Monitoreo físico de los intermediarios de recombinación durante la meiosis de la levadura en ciernes.
- Análisis de mutantes triples deficientes en las tres resoluciones conocidas del HJ (mms4 slx4 yen1).
- Investigar las dependencias genéticas de la formación de cruces en ausencia de resoluciones conocidas.
Principales resultados:
- Las tres endonucleasas identificadas (Mus81-Mms4, Slx1-Slx4, Yen1) contribuyen a la resolución de la HJ in vivo.
- La resolución de la unión de Holliday y el cruce ocurren eficientemente en un mutante triple que carece de estas resoluciones.
- El cruce en este mutante triple es paradójicamente dependiente de la helicasa Sgs1, la nucleasa Exo1 y el complejo Mlh1-Mlh3.
Conclusiones:
- Existe una nueva vía no descrita previamente para la formación de cruces meioticos, que involucra a Sgs1, Exo1 y Mlh1-Mlh3.
- Esta vía Sgs1-Exo1-Mlh1-Mlh3 es la fuente predominante de cruces en levaduras en ciernes y probablemente en mamíferos.
- Los hallazgos redefinen nuestra comprensión de los mecanismos que rigen el control cruzado en la meiosis.
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