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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
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La metiltransferasa Set1 se opone a las funciones de la auroracinasa Ipl1 en la segregación cromosómica
Ke Zhang1, Wenchu Lin, John A Latham
1Program in Genes and Development, Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
Cell
|September 7, 2005
Resumen
La metiltransferasa Set1 regula la segregación cromosómica mediante la modulación del equilibrio entre la quinasa Ipl1 y la fosfatasa Glc7. Esto implica la metilación de la proteína Dam1 kinetochore, revelando nuevas funciones mitóticas para Set1.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La segregación cromosómica adecuada se basa en un equilibrio entre las actividades de Ipl1 Aurora quinasa y Glc7 fosfatasa en la levadura.
- El papel de la metiltransferasa Set1 en la mitosis no se entiende completamente, con funciones conocidas en la transcripción y la modificación de histonas.
Objetivo del estudio:
- Para investigar el papel de la metiltransferasa Set1 en la regulación de la segregación cromosómica.
- Para aclarar el mecanismo por el cual Set1 influye en el equilibrio Ipl1-Glc7.
- Para identificar las nuevas funciones mitóticas de Set1.
Principales métodos:
- Análisis genético que involucra cepas de levadura con mutaciones en SET1, IPL1 y GLC7.
- Análisis bioquímicos para examinar la metilación y fosforilación de proteínas.
- Análisis de la modificación de la proteína Dam1 kinetochore.
Principales resultados:
- La eliminación de SET1 suprime la pérdida de cromosomas en las células de levadura mutantes ipl1-2.
- Las mutaciones simultáneas en SET1 y GLC7 son letales, lo que indica una interacción funcional.
- Set1 media la metilación de las lisinas conservadas en la proteína cinetocoro Dam1.
- La metilación de Dam1 inhibe la fosforilación dependiente de Ipl1 de las serinas cercanas, independientemente de las funciones conocidas de Set1.
- Estos hallazgos ponen de relieve las funciones inesperadas de Set1 en la mitosis.
Conclusiones:
- La metiltransferasa Set1 juega un papel crítico, no reconocido previamente, en la mitosis y la segregación cromosómica.
- El antagonismo entre la metilación de la lisina (por Set1) y la fosforilación de la serina (por Ipl1) es un mecanismo regulador clave que controla la función de las proteínas durante la mitosis.
- Este estudio revela un nuevo mecanismo para la regulación mitótica que involucra modificaciones post-traducionales.
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