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

被引：159

作者：

Dillon, Laura W. ^{[1
]}

Kumar, Pankaj ^{[1
]}

Shibata, Yoshiyuki ^{[1
]}

Wang, Yuh-Hwa ^{[1
]}

Willcox, Smaranda ^{[2
]}

Griffith, Jack D. ^{[2
]}

Pommier, Yves ^{[3
,4
]}

Takeda, Shunichi ^{[5
]}

Dutta, Anindya ^{[1
]}

机构：

[1] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA

[2] Univ N Carolina, Dept Microbiol & Immunol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA

[3] NCI, Lab Mol Pharmacol, NIH, Bethesda, MD 20892 USA

[4] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[5] Kyoto Univ, Japan Sci & Technol Corp, CREST Res Project, Radiat Genet,Fac Med,Sakyo Ku, Yoshida, Kyoto 6068501, Japan

来源：

CELL REPORTS | 2015年 / 11卷 / 11期

关键词：

STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; VERTEBRATE CELLS; HUMAN GENOME; R-LOOPS; DNA; INSTABILITY; TERMINATION; EXPRESSION; INTEGRITY;

D O I：

10.1016/j.celrep.2015.05.020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1749 / 1759

页数：11

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