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Related Concept Videos

Chromosome Replication02:31

Chromosome Replication

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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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A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
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The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
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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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Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
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Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization
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A chromatin structure-based model accurately predicts DNA replication timing in human cells.

Yevgeniy Gindin1, Manuel S Valenzuela, Mirit I Aladjem

  • 1Genetics Branch Center for Cancer Research, Bethesda, MD, USA.

Molecular Systems Biology
|April 1, 2014
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Summary

A new mechanistic model reveals that human DNA replication timing is an emergent phenomenon. This process does not require a specific regulatory mechanism for replication initiation firing sequence.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Computational Biology

Background:

  • Metazoan genome replication occurs in a precise, cell lineage-specific temporal order.
  • The molecular mechanisms controlling genome replication timing remain poorly understood.
  • No active regulatory mechanisms have been identified for the genome replication firing sequence.

Purpose of the Study:

  • To develop a mechanistic model of genome replication.
  • To predict the empirical replication timing program in humans.
  • To identify the determinants of DNA replication initiation.

Main Methods:

  • Developed a mechanistic model of genome replication.
  • Incorporated time-stochastic initiation at well-defined sites.
  • Utilized DNase-hypersensitive sites as genomic landmarks.

Main Results:

  • The model accurately predicts human DNA replication timing.
  • DNase-hypersensitive sites are optimal and independent determinants of replication initiation.
  • Replication initiation is uncoordinated and time-stochastic.

Conclusions:

  • Human DNA replication timing is a robust emergent phenomenon.
  • No specific regulatory mechanism is required for replication initiation firing sequence.
  • The number of replication forks is a key biological parameter.