Evidence that msh1p plays multiple roles in mitochondrial base excision repair.
Mitochondrial DNA is thought to be especially prone to oxidative damage by reactive oxygen species generated through electron transport during cellular respiration. This damage is mitigated primarily by the base excision repair (BER) pathway, one of the few DNA repair pathways with confirmed activity on mitochondrial DNA. Through genetic epistasis analysis of the yeast Saccharomyces cerevisiae, we examined the genetic interaction between each of the BER proteins previously shown to localize to the mitochondria. In addition, we describe a series of genetic interactions between BER components and the MutS homolog MSH1, a respiration-essential gene. We show that, in addition to their variable effects on mitochondrial function, mutant msh1 alleles conferring partial function interact genetically at different points in mitochondrial BER. In addition to this separation of function, we also found that the role of Msh1p in BER is unlikely to be involved in the avoidance of large-scale deletions and rearrangements.
Pogorzala
Leah
L
Department of Biology, University of Rochester, Rochester, New York 14627, USA. esia@mail.rochester.edu
Mookerjee
Shona
S
Sia
Elaine A
EA
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D024101:Mitochondrial Proteins; D008957:Models, Genetic; D009154:Mutation; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C078660:MSH1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D004706:Endodeoxyribonucleases; C083274:Apn1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C101825:NTG1 protein, S cerevisiae; D045643:DNA Repair Enzymes