A role for recombination junctions in the segregation of mitochondrial DNA in yeast

Abstract

In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygotes relative to wild-type mtDNA. This segregation advantage is abolished by mutations in a gene, MGT1, that encodes a recombination junction-resolving enzyme. We show here that resolvase deficiency causes a larger proportion of molecules to be linked together by recombination junctions, resulting in the aggregation of mtDNA into a small number of cytological structures. This change in mtDNA structure can account for the increased mitotic loss of mtDNA and the altered pattern of mtDNA segregation from zygotes. We propose that the level of unresolved recombination junctions influences the number of heritable units of mtDNA.

DNA Content of Individual Mitochondrial Nucleoids Varies Depending on the Culture Conditions of the Yeast Saccharomyces cerevisiae

“…In contrast, cells that were grown anaerobically in the same medium had giant mt-nucleoids in which, on average, 20.3 mtDNA molecules were involved per mt-nucleoid. Because the large aggregates of mt-nucleoids in anaerobically-grown cells resemble the aggregated form of mt-nucleoids in an mgt1 mutant strain which lacked a cruciform cutting endonuclease (Lockshon et al 1995), it is possible that mtDNA molecules are linked by intermediate recombination junctions in cells that reach to the stationary phase in anaerobic conditions. Whereas the size and number of mt-nucleoids distinctly changed between aerobically-grown cells and anaerobicallygrown cells, the total mtDNA content of the cells did not vary markedly.…”

The road to rack and ruin: selecting deleterious mitochondrial DNA variants

“…We know from work in yeasts that hypersuppressiveness depends on the ability of the organism to resolve recombination (Holliday) junctions. The key protein is a Holliday junction resolvase (HJR), CCE1 [39], as it processes the highly interconnected mtDNAs that form in r 2 strains [40]. In the absence of the enzyme, the network of mtDNA cannot be untangled and distributed evenly to daughter cells.…”

DNA Recombination-Initiation Plays a Role in the Extremely Biased Inheritance of Yeast [rho−] Mitochondrial DNA That Contains the Replication Origin ori5

“…cce1-null mutant cells exhibit normal [rho ϩ ] mtDNA inheritance and mtDNA recombination, but the transmission of [rho Ϫ ] mtDNA from the mother cell to the bud is partially blocked. Thus, the effects of the cce1 null mutation on hypersuppressiveness might be due to preferential blockage of the transmission of [rho Ϫ ] mtDNA to daughter cells (i.e., partitioning), rather than to defects in the replication of [rho Ϫ ] mtDNA (31).…”