{
  "id": 10450682,
  "title": "A dedicated motif in human polymerase gamma enables DNA synthesis through replication roadblocks",
  "url": "https://urgent.news/2026/09/28/a-dedicated-motif-in-human-polymerase-gamma-enables-dna-synthesis",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754746v1?rss=1"
  },
  "original_language": "en",
  "account": "Mitochondrial DNA maintenance is critical for cellular stability, and issues with mtDNA replication are connected to various mitochondrial disorders. While Pol{gamma} (DNA polymerase gamma) must navigate duplex junctions and stable secondary structures during replication, the way the human enzyme bypasses these obstacles is not entirely clear. By examining cryo-electron microscopy structures of Pol{gamma} interacting with forked DNA, G-quadruplex DNA and DNA attached to mitochondrial single-stranded DNA-binding protein (mtSSB), researchers have identified a common pathway for template entry along the catcher domain regardless of the substrate and active-site structures. Within this domain, an arginine-rich helix with R1026, R1030 and R1034 forms a Template Stabilising Motif (TSM). Experiments show that disrupting the TSM leads to impaired strand displacement, RNA-DNA hybrid displacement and synthesis through G4-forming sequences, while preserving synthesis on unstructured templates. Single-molecule optical-tweezers experiments also indicate that mechanical destabilization of the fork can restore mutant strand-displacement activity, while force or mtSSB can restore primer-extension kinetics on ssDNA templates. These findings highlight the role of the TSM in sustaining productive template engagement and reveal template stabilization as a shared mechanism that allows Pol{gamma} to overcome structurally varied barriers in mtDNA.",
  "summary": "Mitochondrial DNA (mtDNA) maintenance is essential for cellular homeostasis, and defects in mtDNA replication are linked to a broad spectrum of mitochondrial diseases. During replication, DNA polymerase {gamma} (Pol{gamma}) must traverse duplex junctions and stable secondary structures, yet how the human enzyme overcomes these barriers remains incompletely understood. Here, cryo-electron…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}