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Related Concept Videos

Replication in Eukaryotes01:29

Replication in Eukaryotes

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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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Replication in Prokaryotes01:32

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DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
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DNA Replication02:40

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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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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
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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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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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DNA replication in primary hepatocytes without the six-subunit ORC.

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    The origin recognition complex (ORC) is vital for DNA replication. Primary cells can initiate DNA synthesis without ORC2, challenging previous assumptions about replication initiation.

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    Area of Science:

    • Molecular Biology
    • Cell Biology
    • Genetics

    Background:

    • The origin recognition complex (ORC) is essential for eukaryotic DNA replication initiation.
    • Cancer cell lines can tolerate the loss of individual ORC subunits (ORC1, ORC2, ORC5).
    • ORC1 is dispensable in mouse liver for endo-reduplication, potentially due to CDC6 substitution.

    Purpose of the Study:

    • To investigate the necessity of ORC2 for DNA replication in primary cells.
    • To determine if primary cells can initiate DNA replication without ORC, similar to cancer cells.

    Main Methods:

    • Conditional deletion of ORC2 in mice.
    • Analysis of DNA synthesis and proliferation in mouse embryo fibroblasts and hepatocytes.
    • Simultaneous deletion of ORC1 and ORC2 in mouse livers.

    Main Results:

    • Mouse embryo fibroblasts require ORC2 for proliferation.
    • Mouse hepatocytes can undergo DNA synthesis and endo-reduplication in vitro and in vivo without ORC2.
    • Mouse livers exhibit endo-reduplication without ORC1 and ORC2 during development and after partial hepatectomy.

    Conclusions:

    • Primary cells, like cancer cell lines, can initiate DNA replication without ORC.
    • The MCM2-7 helicase loader can function independently of ORC in certain primary cell contexts.
    • These findings redefine the essentiality of ORC for DNA replication initiation in vivo.