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HLTF Prevents G4 Accumulation and Promotes G4-induced Fork Slowing to Maintain Genome Stability

GSE247967 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 5 samples Submitted 2024/08/13 Platform GPL24676
Summary
G-quadruplexes (G4s) form throughout the genome and influence important cellular processes, but their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected, dual role for the dsDNA translocase HLTF in G4 metabolism. First, we find that HLTF is enriched at G4s in the human genome and suppresses G4 accumulation throughout the cell cycle using its ATPase activity. This function of HLTF affects telomere maintenance by restricting alternative lengthening of telomeres, a process stimulated by G4s. We also show that HLTF and MSH2, a mismatch repair factor that binds G4s, act in independent pathways to suppress G4s and to promote resistance to G4 stabilization. In a second, distinct role, HLTF restrains DNA synthesis upon G4 stabilization by suppressing PrimPol-dependent repriming. Together, the dual functions of HLTF in the G4 response prevent DNA damage and potentially mutagenic replication to safeguard genome stability.
Published in
HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability
Bai G, Endres T, Kühbacher U et al. · Molecular cell 2024 · PMID 39142279 · doi:10.1016/j.molcel.2024.07.018
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Also filed as BioProject PRJNA1041318 and SRA study SRP472358. Searching any of these in the dataset finder brings you back here.

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