Video Experimental Relacionado
Updated: Jun 13, 2026
09:40
Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae
Published on: September 23, 2011
Las secuencias de señales de recombinación restringen la recombinación cromosómica V(D) J más allá de la regla 12/23
C H Bassing1, F W Alt, M M Hughes
1Howard Hughes Medical Institute, Children's Hospital and Department of Genetics, Harvard Medical School and The Center for Blood Research, Boston, Massachusetts 02115, USA.
Nature
|June 13, 2000
Resumen
La regla 12/23 guía la recombinación V(D) J, pero un específico 5' Dbeta1 12-RSS apunta precisamente al reordenamiento del repertorio Vbeta, independientemente de su posición. Este hallazgo impacta la comprensión del ensamblaje genético y el desarrollo de los receptores inmunes.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La recombinación V(D) J ensambla genes receptores de antígenos linfocíticos de los segmentos V, D y J.
- Las proteínas del gen activador de la recombinasa (RAG)-1 y -2 inician la recombinación V(D) J creando roturas de ADN en las secuencias de señales de recombinación (RSS).
- La regla 12/23 dicta la recombinación entre segmentos de genes con 12-RSS y 23-RSS, mediada por el reconocimiento RAG-1/2.
Objetivo del estudio:
- Para investigar el mecanismo de orientación de la reorganización del repertorio Vbeta en el conjunto del locus beta del receptor de células T (TCR).
- Para aclarar el papel de elementos RSS específicos en la recombinación V(D) J más allá de la regla general 12/23.
- Comprender cómo las restricciones adicionales regulan el ensamblaje de genes de región variable y el desarrollo del repertorio inmune.
Principales métodos:
- Se utilizaron células madre embrionarias y ratones genéticamente modificados con un locus TCRbeta simplificado.
- Centrado en un locus con un solo segmento de gen Dbeta (Dbeta1) y un grupo de genes Jbeta (Jbeta1).
- Se analizó el impacto de los 5' Dbeta1 12-RSS y Jbeta1 12-RSS en el reordenamiento del repertorio Vbeta.
Principales resultados:
- Demostrado que el 5' Dbeta1 12-RSS, no el Jbeta1 12-RSS, tiene como objetivo específico el reordenamiento del repertorio Vbeta.
- Se demostró que esta orientación es precisa e independiente de la posición genómica del RSS.
- Se identificó una restricción adicional en la recombinación V(D) J más allá de la regla 12/23 establecida.
Conclusiones:
- El 5' Dbeta1 12-RSS juega un papel crucial en la dirección de la selección del gen Vbeta durante el ensamblaje de TCRbeta.
- Este mecanismo de orientación precisa contribuye a la regulación del ensamblaje de genes de región variable.
- Los hallazgos tienen implicaciones significativas para comprender el desarrollo y la diversidad del repertorio inmune.
Videos de Conceptos Relacionados
01:34Crossing Over
Unlike mitosis, meiosis aims for genetic diversity in its creation of haploid gametes. Dividing germ cells first begin this process in prophase I, where each chromosome—replicated in S phase—is now composed of two sister chromatids (identical copies) joined centrally.
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process called synapsis.
In order to...
02:31Homologous Recombination
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...
02:13Overview of Transposition and Recombination
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
02:31Homologous Recombination
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...
01:30Crossing Over
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...