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Related Concept Videos

The Replisome03:01

The Replisome

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.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
The Replisome03:01

The Replisome

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.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
Lagging Strand Synthesis01:59

Lagging Strand Synthesis

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.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
Lagging Strand Synthesis01:59

Lagging Strand Synthesis

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.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...

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Related Experiment Video

Updated: Jun 21, 2026

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
08:53

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method

Published on: May 2, 2025

Single-molecule analysis reveals that the lagging strand increases replisome processivity but slows replication fork

Nina Y Yao1, Roxana E Georgescu, Jeff Finkelstein

  • 1Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 12, 2009
PubMed
Summary

Individual bacterial DNA replication machines (replisomes) move at steady speeds, but their rates vary widely. Lagging strand synthesis slows leading strand movement but increases overall DNA replication processivity.

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Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome

Published on: September 13, 2024

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Microbiology

Background:

  • DNA replication is crucial for cell division and requires complex molecular machinery called replisomes.
  • Understanding replisome dynamics at the single-molecule level is essential for elucidating DNA synthesis mechanisms.

Purpose of the Study:

  • To investigate the mechanistic features and dynamics of individual Escherichia coli (E. coli) replisomes during long DNA synthesis.
  • To determine the relationship between leading and lagging strand synthesis and their impact on replication fork progression and processivity.

Main Methods:

  • Utilized advanced single-molecule techniques to observe and analyze the behavior of individual E. coli replisomes in real-time.
  • Measured the rates of fork movement and processivity during the synthesis of long DNA molecules.

Main Results:

  • Individual E. coli replisomes exhibit constant rates of fork movement, but significant variability exists between different replisomes.
  • Lagging strand synthesis was found to decrease the rate of leading strand synthesis, indicating a 'drag' effect.
  • Lagging strand synthesis substantially increased the overall processivity of the replisome, suggesting enhanced DNA binding.

Conclusions:

  • Replisome rate variability is a key feature of DNA replication, with implications for genomic stability.
  • The interplay between leading and lagging strand synthesis significantly influences replication fork dynamics and efficiency.
  • Increased replisome processivity, potentially due to dual DNA polymerase engagement, ensures complete DNA synthesis.