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Proofreading
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Proofreading
Overview
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 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...
Translesion DNA Polymerases
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.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Improving Translational Accuracy
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Biophysical journal·2026
Related Experiment Video
Updated: May 8, 2026

07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 29, 2010
Backtracking dynamics of RNA polymerase: pausing and error correction.
1Max Planck Institute of Colloids and Interfaces, Science Park Golm, D-14424 Potsdam, Germany.
Summary
RNA polymerase backtracking pauses transcription. This process aids accuracy and can prevent transcription slowdowns, differing from classical proofreading models.
Area of Science:
- Molecular Biology
- Biophysics
Background:
- Transcription by RNA polymerases is often paused.
- Backtracking is a key pausing mechanism where the polymerase moves backward without shortening the RNA transcript.
Purpose of the Study:
- To present exact results for a kinetic model of backtracking.
- To analyze the impact of backtracking on transcription speed and accuracy.
Main Methods:
- Kinetic modeling of RNA polymerase backtracking.
- Mathematical analysis of transcription dynamics.
Main Results:
- Backtracking offers a proofreading mechanism distinct from the Hopfield-Ninio scheme.
- Backtracking can attenuate transcription slowdowns caused by nucleotide discrimination.
Conclusions:
- Backtracking plays a crucial role in enhancing transcription accuracy.
- Backtracking may have a dual function, improving accuracy and maintaining transcription speed.

