Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Inside the cells of many species, double-stranded DNA is packaged together with specialized proteins to form structures called chromosomes. Breaks that span across both strands of the DNA can cause cell death because if the break is incorrectly repaired, a segment of the DNA may be lost. Cells use a process known as homologous recombination to repair such breaks correctly. This uses an undamaged DNA molecule as a template that can be copied to replace missing segments of the DNA sequence. During the repair of double-strand breaks, connections called crossovers may form. This results in the damaged and undamaged DNA molecules swapping a portion of their sequences. In meiosis, a type of cell division that produces sperm and eggs, cells deliberately break their chromosomes and then repair them using homologous recombination. The crossovers that form during this process are important for sharing chromosomes between the newly forming cells. It is crucial that the crossovers form at the right time and place along the chromosomes. Chromosomes have different structures depending on whether a cell is undergoing meiosis or normal (mitotic) cell division. This structure may influence how and where crossovers form. Enzymes called resolvases catalyze the reactions that occur during the last step in homologous recombination to generate crossovers. One particular resolvase acts only during meiosis, whereas others are active in both mitotic and meiotic cells. However, it is not known whether local features of the chromosome structure – such as the proteins packaged in the chromosome alongside the DNA – influence when and where meiotic crossover occurs. Medhi et al. have now studied how recombination occurs along different regions of the chromosomes in budding yeast cells, which undergo meiosis in a similar way to human cells. The results of the experiments reveal that the mechanism by which crossovers form depends on proteins called axis proteins, one type of which is specifically found in meiotic chromosomes. In regions that had high levels of meiotic axis proteins, crossovers mainly formed using the meiosis-specific resolvase enzyme. In regions that had low levels of meiotic axis proteins, crossovers formed using resolvases that are active in mitotic cells. Further experiments demonstrated that altering the levels of one of the meiotic axis proteins changed which resolvase was used. Overall, the results presented by Medhi et al. show that differences in chromosome structure, in particular the relative concentration of meiotic axis proteins, influence how crossovers form in yeast. Future studies will investigate whether this is observed in other organisms such as humans, and whether local chromosome structure influences other steps of homologous recombination in meiosis.