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Fixing Double-strand Breaks02:04

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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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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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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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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...
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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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Las rupturas de doble hebra del ADN activan un programa genético multifuncional en el desarrollo de los linfocitos.

Andrea L Bredemeyer1, Beth A Helmink, Cynthia L Innes

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Nature
|October 14, 2008
PubMed
Resumen
Este resumen es generado por máquina.

Las rupturas fisiológicas de doble hebra del ADN en los linfocitos activan un amplio programa transcripcional más allá de la reparación del ADN. Esta respuesta influye en el desarrollo de los linfocitos y puede ser interrumpida por el daño genotóxico.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Inmunología Inmunología.
  • Genética La genética.

Sus antecedentes:

  • Las rupturas de doble cadena de ADN (DSB) son lesiones críticas del ADN.
  • Las respuestas celulares a los DSB típicamente involucran puntos de control del ciclo celular y vías de supervivencia.
  • Los DSB se generan intencionalmente durante el desarrollo de los linfocitos para el ensamblaje genético del receptor de antígenos.

Objetivo del estudio:

  • Para investigar la respuesta transcripcional a los DSB fisiológicos durante el desarrollo de los linfocitos.
  • Para determinar si esta respuesta difiere de la respuesta DSB canónica.
  • Explorar las implicaciones para el desarrollo de linfocitos y el daño genotóxico.

Principales métodos:

  • Análisis de la expresión génica en linfocitos murinos.
  • Comparación de los perfiles de transcripción después de la inducción fisiológica y genotóxica de DSB.

Principales resultados:

  • Los DSB fisiológicos en los linfocitos desencadenan un amplio programa transcripcional.
  • Este programa se extiende más allá de los genes de respuesta al daño del ADN canónicos.
  • Muchos genes inducidos están involucrados en diversos procesos celulares cruciales para el desarrollo de los linfocitos.
  • Algunos patrones de expresión génica se superponen entre las respuestas fisiológicas y genotóxicas de la DSB.

Conclusiones:

  • Los DSB fisiológicos actúan como señales de señalización que regulan procesos específicos del tipo de célula más allá del mantenimiento del genoma.
  • Los DSB genotóxicos pueden afectar las funciones celulares normales al interferir con estas vías de desarrollo.
  • Comprender estos distintos programas de transcripción es vital para la biología de los linfocitos y la toxicología.