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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Translesion DNA Polymerases02:10

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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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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Restarting Stalled Replication Forks02:37

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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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The Replisome03:01

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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
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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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Related Experiment Video

Updated: Jul 11, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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CST-Polymeraseα-primase solves a second telomere end-replication problem.

Hiroyuki Takai1, Valentina Aria2, Pamela Borges1

  • 1Laboratory for Cell Biology and Genetics, Rockefeller University, New York, USA.

Biorxiv : the Preprint Server for Biology
|November 14, 2023
PubMed
Summary
This summary is machine-generated.

Telomere shortening is caused by two replication problems. Telomerase maintains the G-strand, while CST-Polymeraseα(Polα)-primase handles the C-strand to prevent telomere attrition.

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Kinetics of Lagging-strand DNA Synthesis In Vitro by the Bacteriophage T7 Replication Proteins
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Kinetics of Lagging-strand DNA Synthesis In Vitro by the Bacteriophage T7 Replication Proteins
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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Telomeres protect chromosome ends from degradation and fusion.
  • Telomere shortening occurs due to the end-replication problem during DNA synthesis.
  • Telomerase counteracts shortening by adding repeats to the G-rich strand.

Approach:

  • Investigated a second end-replication problem affecting the C-rich strand.
  • Utilized in vitro assays to analyze lagging-strand synthesis limitations.
  • Examined telomere length dynamics in cells lacking CST-Polymeraseα(Polα)-primase.

Key Points:

  • Lagging-strand synthesis is incomplete, leaving a gap near the telomere end.
  • CST-Polymeraseα(Polα)-primase fills this gap, maintaining C-strand length.
  • Cells lacking CST-Polα-primase exhibit significant C-strand shortening at lagging ends.

Conclusions:

  • Canonical DNA replication presents two distinct telomere end-replication challenges.
  • Telomerase is essential for G-strand maintenance.
  • CST-Polymeraseα(Polα)-primase is crucial for C-strand maintenance, preventing telomere loss.