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Published on: October 14, 2025
Regression supports two mechanisms of fork processing in phage T4
David T Long1, Kenneth N Kreuzer
1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Summary
Replication forks encountering DNA damage can stall. Bacteriophage T4 origin forks regress, forming structures processed by specific enzymes for reactivation, ensuring DNA synthesis completion.
Area of Science:
- Molecular Biology
- DNA Replication
- Virology
Background:
- DNA replication forks frequently stall due to DNA damage or protein impediments.
- Stalled fork reactivation is crucial for completing DNA synthesis.
- The bacteriophage T4 origin fork serves as a model for studying stalled fork processing.
Purpose of the Study:
- To investigate the in vivo mechanisms of stalled replication fork reactivation.
- To characterize the processing of the bacteriophage T4 origin fork.
- To elucidate the roles of specific T4 proteins in fork resolution.
Main Methods:
- Utilized the bacteriophage T4 origin fork as a model system.
- Analyzed fork structures in vivo using genetic approaches.
- Investigated the function of T4 gene products (gp) 46/47 and EndoVII in fork processing.
Main Results:
- The T4 origin fork undergoes regression in vivo to form a regressed fork structure.
- Fork regression generates both a double-stranded end (DSE) and a Holliday junction.
- T4 gp46/47 and EndoVII process these structures via distinct pathways, leading to fork reactivation.
Conclusions:
- Replication fork regression is a key intermediate in stalled fork reactivation.
- Two independent but potentially cooperative pathways, involving DSE processing and Holliday junction resolution, contribute to reactivation.
- The T4 system provides insights into conserved mechanisms for resolving stalled replication forks.
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