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Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
Published on: September 13, 2024
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Structure of monkeypox virus DNA polymerase holoenzyme
Qi Peng1, Yufeng Xie2, Lu Kuai1
1CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Science (New York, N.Y.)
|December 15, 2022
Summary
Mpox virus DNA replication was elucidated by determining the structure of its polymerase holoenzyme. This finding reveals a "forward sliding clamp" mechanism and may aid in developing new antiviral drugs.
Area of Science:
- Virology
- Structural Biology
- Drug Discovery
Background:
- Mpox (monkeypox) was declared a global health emergency in July 2022, highlighting the urgent need for treatments.
- The mpox virus (MPXV) relies on its DNA polymerase (F8) and cofactors (A22, E4) for genome replication.
Purpose of the Study:
- To determine the structure of the MPXV DNA polymerase holoenzyme bound to DNA.
- To elucidate the mechanism of viral genome replication.
Main Methods:
- Cryo-electron microscopy was used to determine the holoenzyme structure at ~2.8 angstrom resolution.
- Structural analysis focused on DNA binding and polymerase architecture.
Main Results:
- The holoenzyme structure reveals a "forward sliding clamp" mechanism for processive DNA replication.
- MPXV polymerase exhibits a DNA binding mode conserved among B-family polymerases.
Conclusions:
- The study clarifies the MPXV genome replication mechanism.
- Findings provide a structural basis for developing novel anti-poxvirus therapeutics.
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