Intricate and Cell Type-Specific Populations of Endogenous Circular DNA (eccDNA) in Caenorhabditis elegans and Homo sapiens

Author:

Shoura Massa J1,Gabdank Idan1,Hansen Loren1,Merker Jason1,Gotlib Jason2,Levene Stephen D345,Fire Andrew Z16

Affiliation:

1. Department of Pathology, Stanford University School of Medicine, California 94305

2. Department of Hematology, Stanford University School of Medicine, California 94305

3. Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080

4. Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas 75080

5. Department of Physics, University of Texas at Dallas, Richardson, Texas 75080

6. Department of Genetics, Stanford University School of Medicine, California 94305

Abstract

Abstract Investigations aimed at defining the 3D configuration of eukaryotic chromosomes have consistently encountered an endogenous population of chromosome-derived circular genomic DNA, referred to as extrachromosomal circular DNA (eccDNA). While the production, distribution, and activities of eccDNAs remain understudied, eccDNA formation from specific regions of the linear genome has profound consequences on the regulatory and coding capabilities for these regions. Here, we define eccDNA distributions in Caenorhabditis elegans and in three human cell types, utilizing a set of DNA topology-dependent approaches for enrichment and characterization. The use of parallel biophysical, enzymatic, and informatic approaches provides a comprehensive profiling of eccDNA robust to isolation and analysis methodology. Results in human and nematode systems provide quantitative analysis of the eccDNA loci at both unique and repetitive regions. Our studies converge on and support a consistent picture, in which endogenous genomic DNA circles are present in normal physiological states, and in which the circles come from both coding and noncoding genomic regions. Prominent among the coding regions generating DNA circles are several genes known to produce a diversity of protein isoforms, with mucin proteins and titin as specific examples.

Publisher

Oxford University Press (OUP)

Subject

Genetics(clinical),Genetics,Molecular Biology

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