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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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The DNA Replication Fork01:02

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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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Variación genética en el tiempo de replicación del ADN humano.

Amnon Koren1, Robert E Handsaker2, Nolan Kamitaki2

  • 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

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|November 24, 2014
PubMed
Resumen
Este resumen es generado por máquina.

Las variaciones genéticas influyen en el tiempo de replicación del ADN, afectando los patrones de mutación. Este estudio identifica 16 loci genéticos (rtQTLs) que regulan el tiempo de replicación y la expresión génica, impactando la mutabilidad de la secuencia de ADN.

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Área de la Ciencia:

  • Genética La genética.
  • La genómica es la genómica.
  • Biología Molecular Biología Molecular

Sus antecedentes:

  • La replicación del ADN genómico ocurre en un orden temporal específico, lo que influye en la distribución de las mutaciones.
  • La base genética de la variación del tiempo de replicación del ADN no se entiende completamente.

Objetivo del estudio:

  • Para investigar el impacto de los polimorfismos genéticos en el tiempo de replicación del ADN.
  • Para identificar los loci genéticos que controlan la variación del tiempo de replicación.

Principales métodos:

  • Se analizó la variación en el tiempo de replicación utilizando profundidad de lectura en secuencias de genoma de 161 individuos (Proyecto 1000 Genomas).
  • Se realizaron estudios de asociación de todo el genoma para identificar los loci de rasgos cuantitativos de tiempo de replicación (rtQTL).

Principales resultados:

  • Se identificaron 16 loci rtQTL donde los alelos heredados se asocian con el tiempo de replicación.
  • Los rtQTL demuestran efectos específicos del alelo en el tiempo de replicación y el uso del origen.
  • Los rtQTL están asociados con la variación de la expresión génica en escalas de megabases.

Conclusiones:

  • El tiempo de replicación del ADN está significativamente moldeado por los polimorfismos genéticos.
  • Los polimorfismos heredados regulan la mutabilidad de las secuencias de ADN cercanas a través del control del tiempo de replicación.