Figure 3. Asymmetries in DNA replication underlie mating-type switching in S. pombe.

(A) A P-type mating cell entering DNA replication with the mat1 (mating type) locus labeled with blue circle. (A′) The replication fork approaches the mat1 locus. (A″) As replication proceeds, one strand is replicated by continuous (leading strand) synthesis whereas the other strand is replicated by discontinuous (lagging-strand) synthesis, characterized by numerous RNA primers. (A‴) One of these primers fails to get properly removed during lagging strand processing, leaving a molecular lesion (two RNA nucleotides) necessary for mating-type switching to occur. (A‴′) Two sister chromatids now exist: one with a molecular lesion and one which is unmarked. (B–C) The two sister chromatids are segregated to distinct daughter cells during mitosis. (D) Two daughter cells now enter S-phase; one with the molecular lesion and one without. (D′) In the daughter cell with the molecular lesion, the replication fork approaches the mat1 locus. (D″) The replication fork stalls when it hits the lesion. (D‴) The fork is rescued in DNA repair mechanism resembling synthesis dependent strand annealing. The result of this process is that the strand where the collision occurred has new DNA copied into the mat1 locus, resulting in a switch in mating type from P ➔ M. (D‴′) Two sister chromatids are produced; one which has switched mating type, the other which now contains a molecular lesion. (E) Two daughter cells are produced: one which has switch mating type, the other of which has not.