Genome instability triggers intercellular DNA transfer between human cells

2026/05/19 by Elizabeth G. Maurais, Alice Mazzagatti, Yu-Fen Lin +13 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #DNA Repair Mechanisms #Telomeres, Telomerase, and Senescence #Nuclear Structure and Function

paper · doi:10.1016/j.cell.2026.04.041

openalex created_date 2026/05/19 · openalex publication_date 2026/05/19 · openalex updated_date 2026/08/01

Abstract

The mammalian genome is safeguarded within the confines of the interphase nucleus. However, genomic instability can trigger the mislocalization of nuclear DNA to the cytoplasm within micronuclei or as fragmented chromosomes. Beyond activating cell-autonomous signaling programs, whether such cytoplasmic DNA can elicit non-cell-autonomous consequences to nearby cells remains unclear. Here, we show that cytoplasmic DNAs undergo intercellular transfer through contact-dependent, cytoskeleton-based nanotube structures connecting adjacent human cells. Diverse sources of genomic instability-including exposure to mitotic spindle poisons, ionizing radiation, and Cas9-induced chromosome breakage-promote nanotube-mediated DNA transfer in both cancerous and non-cancerous cells. Transferred DNA fragments are stably inherited as functional extrachromosomal genetic elements in the recipient host genome, thereby conferring heritable phenotypic traits to the recipient cell. Our findings uncover a horizontal gene transfer-like mechanism through which direct cell-cell contact can propagate genomic instability and reshape mammalian genomes.

Citations

• Horizontal gene transfer and the evolution of bacterial and archaeal population structure
• Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development
• A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence Imaging
• Mechanisms of gene flow in archaea
• Integrated analysis of multimodal single-cell data
• Intercellular communication in the brain through a dendritic nanotubular network
• Tunneling nanotubes: Reshaping connectivity
• Peering into tunneling nanotubes—The path forward

Discussions

• ... and notably, the transferred DNA is inherited and functional: recipients acquiring a resistance gene became drug-resistant😱 Maurais et al., Ly lab: doi.org/10.1016/j.ce... [bsky, 0 points, 0 comments]