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Yeast EndoG prevents genome instability by degrading extranuclear DNA species.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 03; Vol. 15 (1), pp. 7653. Date of Electronic Publication: 2024 Sep 03. - Publication Year :
- 2024
-
Abstract
- In metazoans mitochondrial DNA (mtDNA) or retrotransposon cDNA released to cytoplasm are degraded by nucleases to prevent sterile inflammation. It remains unknown whether degradation of these DNA also prevents nuclear genome instability. We used an amplicon sequencing-based method in yeast enabling analysis of millions of DSB repair products. In non-dividing stationary phase cells, Pol4-mediated non-homologous end-joining increases, resulting in frequent insertions of 1-3 nucleotides, and insertions of mtDNA (NUMTs) or retrotransposon cDNA. Yeast EndoG (Nuc1) nuclease limits insertion of cDNA and transfer of very long mtDNA ( >10 kb) to the nucleus, where it forms unstable circles, while promoting the formation of short NUMTs (~45-200 bp). Nuc1 also regulates transfer of extranuclear DNA to nucleus in aging or meiosis. We propose that Nuc1 preserves genome stability by degrading retrotransposon cDNA and long mtDNA, while short NUMTs originate from incompletely degraded mtDNA. This work suggests that nucleases eliminating extranuclear DNA preserve genome stability.<br /> (© 2024. The Author(s).)
- Subjects :
- Cell Nucleus metabolism
Cell Nucleus genetics
DNA End-Joining Repair
DNA Breaks, Double-Stranded
Meiosis genetics
Endodeoxyribonucleases metabolism
Endodeoxyribonucleases genetics
Genomic Instability
DNA, Mitochondrial genetics
DNA, Mitochondrial metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Saccharomyces cerevisiae Proteins genetics
Retroelements genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39227600
- Full Text :
- https://doi.org/10.1038/s41467-024-52147-2