Journal
GENOME RESEARCH
Volume 25, Issue 6, Pages 814-824Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.190470.115
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Funding
- Wellcome Trust
- European Molecular Biology Organization long-term fellowship [LTF 1203_2012]
- Marie Curie Fellowship FP7-PEOPLE-IEF [328264]
- National Institute for Health Research (NIHR) UCLH Biomedical Research Centre
- European Union (BASIS)
- Cancer Research UK
- Dallaglio Foundation [C5047/A14835]
- National Institute for Health Research
- Royal Marsden NHS Foundation Trust
- National Cancer Research Prostate Cancer Mechanisms of Progression and Treatment (PROMPT) collaborative in Cambridge [G0500966/75466]
- Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award
- Breakthrough Breast Cancer Research [ICGC 08/09, KCL]
- BBSRC [BBS/E/F/00044431, BBS/E/F/00042686] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/F/00042686, BBS/E/F/00044431] Funding Source: researchfish
- Cancer Research UK [12765, 17528, 16942, 14835, 15007] Funding Source: researchfish
- Cancer Research UK
- Versus Arthritis [20406] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
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Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.
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