Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity

Laura W. Dillon, Pankaj Kumar, Yoshiyuki Shibata, Yuh Hwa Wang, Smaranda Willcox, Jack D. Griffith, Yves Pommier, Shunichi Takeda, Anindya Dutta

    Research output: Contribution to journalArticle

    31 Scopus citations


    MicroDNAs are <400-base extrachromosomal circles found in mammalian cells. Tens of thousands of microDNAs have been found in all tissue types, including sperm. MicroDNAs arise preferentially from areas with high gene density, GC content, and exon density from promoters with activating chromatin modifications and in sperm from the 5'-UTR of full-length LINE-1 elements, but are depleted from lamin-associated heterochromatin. Analysis of microDNAs from a set of human cancer cell lines revealed lineage-specific patterns of microDNA origins. A survey of microDNAs from chicken cells defective in various DNA repair proteins reveals that homologous recombination and non-homologous end joining repair pathways are not required for microDNA production. Deletion of the MSH3 DNA mismatch repair protein results in a significant decrease in microDNA abundance, specifically from non-CpG genomic regions. Thus, microDNAs arise as part of normal cellular physiology-either from DNA breaks associated with RNA metabolism or from replication slippage followed by mismatch repair. Through isolating and sequencing small extrachromosomal circular microDNAs across multiple species and cell types, Dillon et al. identify specific genomic features associated with the generation of microDNAs and link the DNA mismatch repair pathway to this process.

    Original languageEnglish (US)
    Pages (from-to)1749-1759
    Number of pages11
    JournalCell Reports
    Issue number11
    StatePublished - Jun 23 2015


    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Dillon, L. W., Kumar, P., Shibata, Y., Wang, Y. H., Willcox, S., Griffith, J. D., Pommier, Y., Takeda, S., & Dutta, A. (2015). Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity. Cell Reports, 11(11), 1749-1759.