Roles for the Rad27 flap endonuclease in mitochondrial mutagenesis and double-strand break repair in Saccharomyces cerevisiae

Prabha Nagarajan, Christopher T. Prevost, Alexis Stein, Rachel Kasimer, Lidza Kalifa, Elaine A. Sia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The structure-specific nuclease, Rad27p/FEN1, plays a crucial role in DNA repair and replication mechanisms in the nucleus. Genetic assays using the rad27-Δ mutant have shown altered rates of DNA recombination, microsatellite instability, and point mutation in mitochondria. In this study, we examined the role of Rad27p in mitochondrial mutagenesis and double-strand break (DSB) repair in Saccharomyces cerevisiae. Our findings show that Rad27p is essential for efficient mitochondrial DSB repair by a pathway that generates deletions at a region flanked by direct repeat sequences. Mutant analysis suggests that both exonuclease and endonuclease activities of Rad27p are required for its role in mitochondrial DSB repair. In addition, we found that the nuclease activities of Rad27p are required for the prevention of mitochondrial DNA (mtDNA) point mutations, and in the generation of spontaneous mtDNA rearrangements. Overall, our findings underscore the importance of Rad27p in the maintenance of mtDNA, and demonstrate that it participates in multiple DNA repair pathways in mitochondria, unlinked to nuclear phenotypes.

Original languageEnglish (US)
Pages (from-to)843-857
Number of pages15
JournalGenetics
Volume206
Issue number2
DOIs
StatePublished - Jun 2017

Keywords

  • DNA repair
  • Double-strand break
  • Mitochondria
  • mtDNA

ASJC Scopus subject areas

  • General Medicine

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