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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.
Many Proteins Orchestrate Replication at the 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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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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Homologous Recombination02:31

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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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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).
Two states at the origin of replication
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Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
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Related Experiment Video

Updated: Aug 4, 2025

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

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ERCC6L2 mitigates replication stress and promotes centromere stability.

Christopher J Carnie1, Lucy Armstrong1, Marek Sebesta1

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Cell Reports
|April 4, 2023
PubMed
Summary
This summary is machine-generated.

ERCC6L2 is identified as a key regulator of centromeric chromatin reassembly after DNA replication. Its absence leads to uncontrolled centromeric DNA replication and chromatin erosion, impacting genomic stability.

Keywords:
CP: Molecular biologyDNA repairERCC6L2IBMFSPCNAPIP-boxSNF2 ATPasecentromerechromatinend resectionreplication stress

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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Centromeres are crucial for chromosome segregation but are difficult to replicate.
  • The precise mechanisms of centromeric chromatin assembly post-replication remain largely unknown.
  • Understanding these processes is vital for genomic stability and disease research.

Purpose of the Study:

  • To identify key regulators of centromeric chromatin reassembly.
  • To elucidate the function of ERCC6L2 in DNA replication and repair.
  • To provide a mechanistic model for ERCC6L2's diverse roles.

Main Methods:

  • Cellular localization studies of ERCC6L2.
  • Analysis of ERCC6L2 knockout (ERCC6L2-/-) cells.
  • Co-crystal structure determination of ERCC6L2 with PCNA.
  • DNA repair assays, including DNA end resection analysis.

Main Results:

  • ERCC6L2 accumulates at centromeres and facilitates the deposition of core centromeric factors.
  • ERCC6L2-/- cells exhibit unrestrained centromeric DNA replication and chromatin erosion.
  • ERCC6L2 promotes replication at genomic repeats and non-canonical DNA structures.
  • ERCC6L2 interacts with PCNA via an atypical peptide and restricts DNA end resection independently of the 53BP1 pathway.

Conclusions:

  • ERCC6L2 is a critical regulator of centromeric chromatin replication and stability.
  • ERCC6L2 integrates roles in DNA replication, repair, and maintenance of genomic structures.
  • These findings offer molecular insights into ERCC6L2's links to human diseases.