Programmed genome rearrangements in Oxytricha produce transcriptionally active extrachromosomal circular DNA

被引:30
|
作者
Yerlici, V. Talya [1 ,2 ]
Lu, Michael W. [1 ,3 ]
Hoge, Carla R. [3 ]
Miller, Richard, V [1 ,2 ]
Neme, Rafik [1 ,5 ]
Khurana, Jaspreet S. [1 ]
Bracht, John R. [4 ]
Landweber, Laura F. [1 ,3 ]
机构
[1] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA
[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
[3] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
[4] Amer Univ, Dept Biol, Washington, DC 20016 USA
[5] Univ Norte, Dept Chem & Biol, Barranquilla, Atlantico, Colombia
基金
美国国家卫生研究院;
关键词
RNA-POLYMERASE-II; CILIATE OXYTRICHA; PRECISE EXCISION; SEQUENCE; DELETION; ELEMENTS; ELIMINATION; PROTEIN; GENES; AMPLIFICATION;
D O I
10.1093/nar/gkz725
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Extrachromosomal circular DNA (eccDNA) is both a driver of eukaryotic genome instability and a product of programmed genome rearrangements, but its extent had not been surveyed in Oxytricha, a ciliate with elaborate DNA elimination and translocation during development. Here, we captured rearrangement-specific circular DNA molecules across the genome to gain insight into its processes of programmed genome rearrangement. We recovered thousands of circularly excised Tc1/mariner-type transposable elements and high confidence non-repetitive germline-limited loci. We verified their bona fide circular topology using circular DNA deep-sequencing, 2D gel electrophoresis and inverse polymerase chain reaction. In contrast to the precise circular excision of transposable elements, we report widespread heterogeneity in the circular excision of non-repetitive germline-limited loci. We also demonstrate that circular DNAs are transcribed in Oxytricha, producing rearrangement-specific long non-coding RNAs. The programmed formation of thousands of eccDNA molecules makes Oxytricha a model system for studying nucleic acid topology. It also suggests involvement of eccDNA in programmed genome rearrangement.
引用
收藏
页码:9741 / 9760
页数:20
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