Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity
Year: 2015
Type: article
Abstract: 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.
Source: Cell Reports
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Defense, Ovarian Cancer Research Fund, Hope Foundation, National Institutes of Health, U.S. Public Health Service, University of Texas MD Anderson Cancer Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences
Awards: G1298195085, G1940195166, G204765997, G2495002360, G2774293502, G2868078262, Signaling and Progression in Prostate Cancer, Genome-wide DNA Secondary Structure Analysis to Investigate DNA Fragility, DNA-Protein Interactions at the Replication Fork, G411726150, G4119534169, G5850682332, G6047344841, DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer Drugs, Effect of anti-S phase agents on human chromosomes, Nucleoprotein Structures at Telomeres and Sites of DNA Damage, EXPLORING THE PRESENCE OF MICRODNA'S IN PROSTATE CANCER CELL LINES, TISSUE, AND SERA OF PROSTATE CANCER PATIENTS AND ITS POSSIBLE APPLICATION AS BIOM, G8612775243, G8632625050, G9000030351, G9000173957, Viral Oncogenesis, Latency, and Replication, University of Virginia Cancer Center Support Grant
OpenAlex ID: W1580824804