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Updated: Jun 17, 2025
11:25
A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
Published on: March 18, 2017
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HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability
Gongshi Bai1, Theresa Endres1, Ulrike Kühbacher1
1Department of Chemical & Systems Biology, Stanford University, Stanford, CA 94305, USA.
Molecular Cell
|August 14, 2024
Summary
The helicase-like transcription factor (HLTF) unfolds G-quadruplexes (G4s) to maintain genome stability. HLTF works with MSH2 to prevent G4 accumulation and DNA damage.
Area of Science:
- Genomics
- Molecular Biology
- DNA Replication
Background:
- G-quadruplexes (G4s) are DNA structures influencing cellular processes.
- Deregulation of G4s can impede DNA replication and compromise genome stability.
Purpose of the Study:
- To investigate the role of the dsDNA translocase HLTF in responding to G4 structures.
- To elucidate the mechanisms by which HLTF maintains genome stability in the presence of G4s.
Main Methods:
- In vitro G4 unfolding assays using HLTF.
- Genome-wide analysis of HLTF enrichment at G4s.
- Synergistic studies involving MSH2 and HLTF.
- Analysis of HLTF's role in suppressing PrimPol-dependent repriming.
Main Results:
- HLTF is enriched at G4s and directly unfolds them in an ATP-dependent manner.
- HLTF suppresses G4 accumulation throughout the cell cycle.
- HLTF and MSH2 synergistically suppress G4 accumulation, restrict ALT, and enhance drug resistance.
- HLTF restrains DNA synthesis by inhibiting PrimPol-dependent repriming when G4s are stabilized.
Conclusions:
- HLTF plays a dual role in the G4 response: unfolding G4s and regulating DNA synthesis.
- These functions collectively prevent DNA damage and mutagenic replication, safeguarding genome stability.
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