Microhomology-Mediated Circular DNA Formation from Oligonucleosomal Fragments During Spermatogenesis
Year: 2023
Type: preprint
Abstract: The landscape of extrachromosomal circular DNA (eccDNA) during mammalian spermatogenesis, as well as the biogenesis mechanism remains to be explored. Here, we revealed widespread eccDNA formation in human sperms and mouse spermatogenesis. We noted that germline eccDNAs are derived from oligonucleosomal DNA fragmentation in cells likely undergoing cell death, providing a potential new way for quality assessment of human sperms. Interestingly, small-sized eccDNAs are associated with euchromatin, while large-sized ones are preferentially generated from heterochromatin. By comparing sperm eccDNAs with meiotic recombination hotspots and structural variations, we found that they are barely associated with de novo germline deletions. We further developed a bioinformatics pipeline to achieve nucleotide-resolution eccDNA detection even with the presence of microhomologous sequences that interfere with precise break-point identification. Empowered by our method, we provided strong evidence to show that microhomology-mediated end joining is the major eccDNA biogenesis mechanism. Together, our results shed lights on eccDNA biogenesis mechanism in mammalian germline cells.
Source: eLife
Institutions: University of California, Los Angeles, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Peking University Third Hospital, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Peking University First Hospital, Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4387399339