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
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
收藏
页码:1749 / 1759
页数:11
相关论文
共 26 条
[1]   DNA ligase IV-deficient cells are more resistant to ionizing radiation in the absence of Ku70: Implications for DNA double-strand break repair [J].
Adachi, N ;
Ishino, T ;
Ishii, Y ;
Takeda, S ;
Koyama, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (21) :12109-12113
[2]   Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability [J].
Beckmann, Jacques S. ;
Estivill, Xavier ;
Antonarakis, Stylianos E. .
NATURE REVIEWS GENETICS, 2007, 8 (08) :639-646
[3]   Reduced X-ray resistance and homologous recombination frequencies in a RAD54(-/-) mutant of the chicken DT40 cell line [J].
Bezzubova, O ;
Silbergleit, A ;
YamaguchiIwai, Y ;
Takeda, S ;
Buerstedde, JM .
CELL, 1997, 89 (02) :185-193
[4]   DEVELOPMENTAL AND CELL-TYPE SPECIFICITY OF LINE-1 EXPRESSION IN MOUSE TESTIS - IMPLICATIONS FOR TRANSPOSITION [J].
BRANCIFORTE, D ;
MARTIN, SL .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (04) :2584-2592
[5]   Extrachromosomal Circular DNA in Eukaryotes: Possible Involvement in the Plasticity of Tandem Repeats [J].
Cohen, S. ;
Segal, D. .
CYTOGENETIC AND GENOME RESEARCH, 2009, 124 (3-4) :327-338
[6]   Recurrent DNA inversion rearrangements in the human genome [J].
Flores, Margarita ;
Morales, Lucia ;
Gonzaga-Jauregui, Claudia ;
Dominguez-Vidana, Rocio ;
Zepeda, Cinthya ;
Yanez, Omar ;
Gutierrez, Maria ;
Lemus, Tzitziki ;
Valle, David ;
Avila, Ma. Carmen ;
Blanco, Daniel ;
Medina-Ruiz, Sofia ;
Meza, Karla ;
Ayala, Erandi ;
Garcia, Delfino ;
Bustos, Patricia ;
Gonzalez, Victor ;
Girard, Lourdes ;
Tusie-Luna, Teresa ;
Davila, Guillermo ;
Palacios, Rafael .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (15) :6099-6106
[7]   Human genetic variation and its contribution to complex traits [J].
Frazer, Kelly A. ;
Murray, Sarah S. ;
Schork, Nicholas J. ;
Topol, Eric J. .
NATURE REVIEWS GENETICS, 2009, 10 (04) :241-251
[8]   GC skew at the 5′ and 3′ ends of human genes links R-loop formation to epigenetic regulation and transcription termination [J].
Ginno, Paul A. ;
Lim, Yoong Wearn ;
Lott, Paul L. ;
Korf, Ian ;
Chedin, Frederic .
GENOME RESEARCH, 2013, 23 (10) :1590-1600
[9]   Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions [J].
Guelen, Lars ;
Pagie, Ludo ;
Brasset, Emilie ;
Meuleman, Wouter ;
Faza, Marius B. ;
Talhout, Wendy ;
Eussen, Bert H. ;
de Klein, Annelies ;
Wessels, Lodewyk ;
de Laat, Wouter ;
van Steensel, Bas .
NATURE, 2008, 453 (7197) :948-U83
[10]   Similar effects of BRCA2 truncation and Rad51 paralog deficiency on immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination [J].
Hatanaka, A ;
Yamazoe, M ;
Sale, JE ;
Takata, M ;
Yamamoto, K ;
Kitao, H ;
Sonoda, E ;
Kikuchi, K ;
Yonetani, Y ;
Takeda, S .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (03) :1124-1134