Genome Rewiring in Time and Space

Abstract: Genomes are not static! They are dynamic and modify their content and architecture in response to intrinsic and extrinsic signals. Genome dynamics have direct phenotypic consequences in terms of cellular development, programmed function, and disease. Although the genome is classically depicted as linear strings, endogenous Extrachromosomal-circular DNA (eccDNA) comprises DNA products of "genome rewiring" in eukaryotic cells. By becoming physically unlinked from their cognate linear chromosomes, these elements become freed from the constraints of linear linkage, copy-number regulation, and equal partitioning to daughter cells. Thus, these circular elements are direct contributors to genomic diversity and cellular heterogeneity; rendering this process of their formation a remarkable vehicle for rapid cellular evolution. Yet, our understanding of genome rewiring via circular-DNA formation remains a fragmentary aspect of the 4D genome. Using a new DNA-topology-centered genomics workflows (in conjunction with new informatics and AI/ML approaches) to investigate eccDNA-mediated genetic diversity, we have identified various pathology-specific regions of rewired chromosomes in normal and cancer backgrounds. In general, this work resurrects and advances the eccDNA field in addition to providing a missing key element for understanding oncogenic heterogeneity, consideration of which may drive novel diagnostics and reevaluation of current therapies.

geometric topology

Audience: researchers in the topic

GEOTOP-A seminar

Series comments: Web-seminar series on Applications of Geometry and Topology