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Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation
Xiaomeng Jia1,2, Xiang Gao1,2, Shuming Zhang1,2
1Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853, USA.
Biorxiv : the Preprint Server for Biology
|October 28, 2024
Summary
DNA replication involves a rotating replisome facing topological challenges. This study reveals the replisome is a powerful torsional motor, crucial for maintaining DNA fork integrity under stress.
Area of Science:
- Molecular Biology
- Biophysics
Background:
- DNA replication requires replisome rotation, causing topological stress.
- Understanding replisome mechanics under torsion is limited.
Purpose of the Study:
- To develop a real-time assay for monitoring DNA replisome movement under torsion.
- To investigate how torsional stress affects replisome progression and function.
Main Methods:
- Developed a label-free, high-resolution, real-time assay.
- Visualized DNA rotation and measured replisome stalling torque.
Main Results:
- The combined helicase and DNA polymerase (DNAP) replisome is a potent torsional motor, generating ~22 pN·nm torque.
- Helicase-DNAP interaction stabilizes the replication fork during stalling.
- Prolonged stalling can inactivate the replisome, but DNAP exchange facilitates restart.
Conclusions:
- The replisome acts as a powerful torsional motor, with synergistic helicase-DNAP action crucial for fork integrity.
- Torsion is a significant regulator of DNA replication stalling and reactivation.
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