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Programmed genome rearrangements in Oxytricha produce transcriptionally active extrachromosomal circular DNA.


ABSTRACT: 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.

SUBMITTER: Yerlici VT 

PROVIDER: S-EPMC6765146 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Programmed genome rearrangements in Oxytricha produce transcriptionally active extrachromosomal circular DNA.

Yerlici V Talya VT   Lu Michael W MW   Hoge Carla R CR   Miller Richard V RV   Neme Rafik R   Khurana Jaspreet S JS   Bracht John R JR   Landweber Laura F LF  

Nucleic acids research 20191001 18


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 el  ...[more]

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