The mechanism of fission yeast mating-type interconversion: evidence for two types of epigenetically inherited chromosomal imprinted events.

Mating types of the fission yeast S. pombe interchange such that only one cell among four granddaughters of a cell ever switches, and the sister of the newly switched cell switches efficiently in consecutive cell divisions, thereby producing chains of recurrent switching. The developmental program is known to be mediated through specific parental chromosomal DNA-strand inheritance at the mating-type locus (mat1). A heritable DNA strand- and sequence-specific imprinting event was previously postulated to be required to cleave the chromosome at mat1 to initiate recombination required for switching. The pedigree analysis presented here demonstrates that swi1, swi3, and swi7 genes are required for the DNA cleavage step directly, and not for the imprinting function, since mutations in these genes reduce the efficiency of initial (i.e., switching of one in four granddaughters) and recurrent switching equally. However, when the mat1 gene sequence is placed adjacent to the indigenous mat1 locus, apparently it is imprinted inefficiently, since recurrent switches of the inserted locus occur nearly five times more often than the initial switches. This "runaway switching" is the first evidence formally demonstrating both the existence of and the requirement for an imprinted mat1 DNA, making it cleavable and consequently swichable. Second, the double-stranded break constitutes another imprinted event as it is evidenced to be inherited from the parental cell.