Genome instability triggers intercellular DNA transfer between human cells
9 affiliations
- 1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 2Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
- 3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 4Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- 5Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
- 6Institute of Molecular Biology, 55128 Mainz, Germany
- 7Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA
- 8Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA
- 9European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, UK; Somatic Genomics Programme, Wellcome Sanger Institute, Hinxton, Cambridge, UK
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.
Related
- Uracil overload triggers global genome instability and dUTPdysgenesis
- Intercellular GAS6-AXL signaling triggers podocyte cuproptosis in acute kidney injury upstream regulated by CEBPD
- Intercellular Transfer of CD155 Mediated by Melanoma Extracellular Vesicles Downregulates DNAM-1 Expression on NK Cells.
- Canavanine-based assay for gross chromosomal rearrangements reveals genome instability hotspots and modulating genes in fission yeast
- Mitochondrial genome instability disrupts brown adipose tissue through pseudohypoxia-iron-NAD⁺ axis
BibTeX
@article{maurais2026genome,
title = {{Genome instability triggers intercellular DNA transfer between human cells}},
author = {Elizabeth G. Maurais and Alice Mazzagatti and Yu-Fen Lin and Maria Narożna and Qing Hu and Rashmi Dahiya and Derek Santiago-Ferrer and Conor P. Herlihy and Mary Krebs and Nikoleta Pateraki and Evlampia Parcharidou and Stamatis Papathanasiou and Brian J. Beliveau and Gary J. Gorbsky and Isidro Cortés‐Ciriano and Peter Ly},
journal = {Cell},
year = {2026},
month = may,
doi = {10.1016/j.cell.2026.04.041},
url = {https://doi.org/10.1016/j.cell.2026.04.041},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genome instability triggers intercellular DNA transfer between human cells
AU - Elizabeth G. Maurais
AU - Alice Mazzagatti
AU - Yu-Fen Lin
AU - Maria Narożna
AU - Qing Hu
AU - Rashmi Dahiya
AU - Derek Santiago-Ferrer
AU - Conor P. Herlihy
AU - Mary Krebs
AU - Nikoleta Pateraki
AU - Evlampia Parcharidou
AU - Stamatis Papathanasiou
AU - Brian J. Beliveau
AU - Gary J. Gorbsky
AU - Isidro Cortés‐Ciriano
AU - Peter Ly
PY - 2026
DA - 2026/05/19
JO - Cell
DO - 10.1016/j.cell.2026.04.041
UR - https://doi.org/10.1016/j.cell.2026.04.041
AB - 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.
SN - 0092-8674
SN - 1097-4172
ER -