Language
English
Publication Date
12-13-2023
Journal
bioRxiv
DOI
10.1101/2023.12.13.571550
PMID
38168242
PMCID
PMC10760121
PubMedCentral® Posted Date
12-13-2023
PubMedCentral® Full Text Version
Pre-Print
Abstract
In metazoans release of mitochondrial DNA or retrotransposon cDNA to cytoplasm can cause sterile inflammation and disease. Cytoplasmic nucleases degrade these DNA species to limit inflammation. It remains unknown whether degradation these DNA also prevents nuclear genome instability. To address this question, we decided to identify the nuclease regulating transfer of these cytoplasmic DNA species to the nucleus. We used an amplicon sequencing-based method in yeast enabling analysis of millions of DSB repair products. Nu clear mt DNA (NUMTs) and retrotransposon cDNA insertions increase dramatically in nondividing stationary phase cells. Yeast EndoG (Nuc1) nuclease limits insertions of cDNA and transfer of very long mtDNA (>10 kb) that forms unstable circles or rarely insert in the genome, but it promotes formation of short NUMTs (∼45-200 bp). Nuc1 also regulates transfer of cytoplasmic DNA to nucleus in aging or during meiosis. We propose that Nuc1 preserves genome stability by degrading retrotransposon cDNA and long mtDNA, while short NUMTs can originate from incompletely degraded mtDNA. This work suggests that nucleases eliminating cytoplasmic DNA play a role in preserving genome stability.
Published Open-Access
yes
Recommended Citation
Yu, Yang; Wang, Xin; Fox, Jordan; et al., "Yeast EndoG Prevents Genome Instability by Degrading Cytoplasmic DNA" (2023). Faculty, Staff and Students Publications. 8100.
https://digitalcommons.library.tmc.edu/baylor_docs/8100