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Nucleotide Excision Repair

Nucleotide Excision Repair

Mutations

Mutations

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

Mutations

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

Nucleotide Excision Repair

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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

DNA Damage Can Stall the Cell Cycle

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

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Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions

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Published on: November 12, 2017

Daño en el ADN por fasicularina.

Sanjay Dutta¹, Hideki Abe, Sakae Aoyagi

¹School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Journal of the American Chemical Society

|October 27, 2005

Resumen

La fasicularina, un nuevo alcaloide de chorros de mar, daña el ADN al alquilar los residuos de guanina. Este compuesto natural forma un ion aziridinium, similar a ciertos fármacos de quimioterapia, ofreciendo nuevos conocimientos sobre los productos naturales que dañan el ADN.

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Área de la Ciencia:

Química de Productos Naturales Química de Productos Naturales
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

Fasicularin es un nuevo alcaloide que contiene tiocianato aislado de la ascidiana * Nephteis fasicularis *.
Estudios anteriores sugirieron que la fasicularina exhibe propiedades citotóxicas potencialmente a través del daño del ADN.

Objetivo del estudio:

Para dilucidar el mecanismo por el cual la fasicularina induce daño al ADN.
Para caracterizar las especies químicas involucradas en la escisión del ADN mediada por fasicularina.

Principales métodos:

Análisis de secuencia en gel de un duplex de ADN marcado con 5'-32P tratado con fasicularina.
Análisis bioquímicos para identificar lesiones en el ADN y reactivos intermedios.

Principales resultados:

El tratamiento con fasicularina causó la escisión selectiva de las hebras en los residuos de guanina en el ADN.
El mecanismo de daño del ADN implica la alquilación de la guanina por un ion aziridinium derivado de la fasicularina.
Esta formación de iones de aziridinio es análoga a la de los agentes alquiladores anticancerígenos utilizados clínicamente.

Conclusiones:

La fasicularina es el primer producto natural identificado para generar un ion de aziridinio que alquila el ADN.
El mecanismo de acción de la fasicularina proporciona un nuevo modelo de producto natural para la alquilación del ADN relevante para el desarrollo de fármacos contra el cáncer.