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Updated: Jul 5, 2025
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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
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USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication
Biorxiv : the Preprint Server for Biology
|January 23, 2024
Summary
The inactive protease USP50 is crucial for DNA replication and fork stability by balancing helicase and nuclease activities. USP50 depletion impairs replication and fork restart, mediated by other helicases and nucleases.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Mammalian DNA replication relies on RecQ helicases for genetic stability.
- The coordination between helicase and nuclease activities during DNA replication is not fully understood.
Approach:
- Identified USP50 (inactive ubiquitin-specific protease) as a ubiquitin-binding, chromatin-associated protein essential for DNA replication.
- Investigated USP50's role in supporting WRN:FEN1, suppressing MUS81-dependent fork collapse, and restricting DNA breaks.
- Analyzed the impact of USP50 depletion on DNA2, RECQL4, and RECQL5 foci and replication defects.
Key Points:
- USP50 is vital for ongoing replication, fork restart, telomere maintenance, and survival under replicative stress.
- USP50 facilitates WRN:FEN1 activity at stalled forks and prevents MUS81-mediated fork collapse.
- USP50 depletion leads to increased DNA2 and RECQL4 foci, with DNA2, RECQL4, and RECQL5 mediating replication defects.
Conclusions:
- USP50 plays a critical role in maintaining genome stability during DNA replication.
- A novel ubiquitin-dependent pathway involving USP50 regulates the balance of helicase and nuclease activities.
- This pathway is essential for managing both ongoing and stalled replication forks.
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