Meiotic versus mitotic recombination: two different routes for double-strand break repair: the different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes

Abstract

Studies in the yeast Saccharomyces cerevisiae have validated the major features of the double-strand break repair (DSBR) model as an accurate representation of the pathway through which meiotic crossovers (COs) are produced. This success has led to this model being invoked to explain double-strand break (DSB) repair in other contexts. However, most non-crossover (NCO) recombinants generated during S. cerevisiae meiosis do not arise via a DSBR pathway. Furthermore, it is becoming increasingly clear that DSBR is a minor pathway for recombinational repair of DSBs that occur in mitotically-proliferating cells and that the synthesis-dependent strand annealing (SDSA) model appears to describe mitotic DSB repair more accurately. Fundamental dissimilarities between meiotic and mitotic recombination are not unexpected, since meiotic recombination serves a very different purpose (accurate chromosome segregation, which requires COs) than mitotic recombination (repair of DNA damage, which typically generates NCOs).

Figure 1

Models for double-strand break repair. A: In the canonical double-strand break repair (DSBR) model proposed by Szostak et al. [6], an initiating DSB is processed to produce 3′ overhangs. One or both of these overhangs can invade a homologous duplex, usually a sister chromatid or homologous chromosome. A D-loop is displaced by the invading strand. The free 3′ end of the invading strand primes synthesis using the homologous sequence as a template. The other resected end of the break anneals to the D-loop, in a process called second-end capture. Additional synthesis and ligation of nicks produces a dHJ intermediate. To resolve the dHJ, two strands are nicked at each of the HJs. If two strands are each nicked twice (once at each junction), NCO repair products are produced. If different strands are cut at each junction (so that each of the four strands is nicked once), CO repair products are produced. B: In synthesis-dependent strand annealing (SDSA), the invading strand is displaced from the D-loop structure and its newly synthesized sequence anneals to the other side of the break. This yields a NCO repair product. C: In dHJ-dissolution, the two HJs are branch-migrated together and then decatenated to produce a NCO.

Figure 2

Meiotic and mitotic recombination are fundamentally different in several aspects, including function, initiating lesions, timing during the cell cycle, and outcome. In this figure, a single pair of homologous chromosomes is shown in each nucleus. Both DNA strands of each chromatid are shown.