HYPERACTIVE RECOMBINATION IN THE MITOCHONDRIAL-DNA OF THE NATURAL DEATH NUCLEAR MUTANT OF NEUROSPORA-CRASSA

In Neurospora crassa, a recessive mutant allele of a nuclear gene, nd (natural death), causes rapid degeneration of the mitochondrial DNA, a process that is manifested phenotypically as an accelerated form of s enescence in growing and stationary mycelia. To examine the mechanisms that are involved in the degradation of the mitochondrial chromosome, several mitochondrial DNA restriction fragments unique to the natural -death mutant were cloned and characterized through restriction, hybri dization, and nucleotide sequence analyses. All of the cloned DNA piec es contained one to four rearrangements that were generated by unequal crossing-over between direct repeats of several different nucleotide sequences that occur in pairs and are dispersed throughout the mitocho ndrial chromosome of wild-type Neurospora strains. The most abundant r epeats, a family of GC-rich sequences that includes the so-called PstI palindromes, were not involved in the generation of deletions in the nd mutant. The implication of these results is that the nd allele hype ractivates a general system for homologous recombination in the mitoch ondria of N. crassa. Therefore, the nd+ allele either codes for a comp onent of the complex of proteins that catalyzes recombination, and pos sibly repair and replication, of the mitochondrial chromosome or speci fies a regulatory factor that controls the synthesis or activity of at least one enzyme or ancillary factor that is affiliated with mitochon drial DNA metabolism.