NDLI: Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes

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Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes

Content Provider	Springer Nature Link
Author	Mittra, Indraneel Khare, Naveen Kumar Raghuram, Gorantla Venkata Chaubal, Rohan Khambatti, Fatema Gupta, Deepika Gaikwad, Ashwini Prasannan, Preeti Singh, Akshita Iyer, Aishwarya Singh, Ankita Upadhyay, Pawan Nair, Naveen Kumar Mishra, Pradyumna Kumar Dutt, Amit
Copyright Year	2015
Abstract	Whether nucleic acids that circulate in blood have any patho-physiological functions in the host have not been explored. We report here that far from being inert molecules, circulating nucleic acids have significant biological activities of their own that are deleterious to healthy cells of the body. Fragmented DNA and chromatin (DNAfs and Cfs) isolated from blood of cancer patients and healthy volunteers are readily taken up by a variety of cells in culture to be localized in their nuclei within a few minutes. The intra-nuclear DNAfs and Cfs associate themselves with host cell chromosomes to evoke a cellular DNA-damage-repair-response (DDR) followed by their incorporation into the host cell genomes. Whole genome sequencing detected the presence of tens of thousands of human sequence reads in the recipient mouse cells. Genomic incorporation of DNAfs and Cfs leads to dsDNA breaks and activation of apoptotic pathways in the treated cells. When injected intravenously into Balb/C mice, DNAfs and Cfs undergo genomic integration into cells of their vital organs resulting in activation of DDR and apoptotic proteins in the recipient cells. Cfs have significantly greater activity than DNAfs with respect to all parameters examined, while both DNAfs and Cfs isolated from cancer patients are more active than those from normal volunteers. All the above pathological actions of DNAfs and Cfs described above can be abrogated by concurrent treatment with DNase I and/or anti-histone antibody complexed nanoparticles both in vitro and in vivo. Taken together, our results that circulating DNAfs and Cfs are physiological, continuously arising, endogenous DNA damaging agents with implications to ageing and a multitude of human pathologies including initiation of cancer.
Starting Page	91
Ending Page	111
Page Count	21
File Format	PDF
ISSN	02505991
Journal	Journal of Biosciences
Volume Number	40
Issue Number	1
e-ISSN	09737138
Language	English
Publisher	Springer India
Publisher Date	2015-02-28
Publisher Institution	Indian Academy of Sciences
Publisher Place	New Delhi
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ageing apoptosis cancer circulating chromatin circulating DNA circulating nucleic acids circulating nucleosomes DNA damage DNA damage response DNA double-strand breaks DNA repair Life Sciences Biomedicine general Zoology Plant Sciences Microbiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology Agricultural and Biological Sciences

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