DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

Forms and abundance of chaperone proteins influence yeast prion variant competition.

[PSI+ ] variants are different infectious conformations of the same Sup35 protein. We show that when [PSI+ ] variants VK and VL co-infect a dividing host, only one prevails in the end and the host genetic background is involved in winner selection. In the 5V-H19 background, the VK variant dominates over the VL variant. The order of dominance is reversed in the 74-D694 background, where VL can coexists with VK for a short period, but will eventually take over. Differential interaction of chaperone proteins with distinct prion variant conformations can influence the outcome of competition. Expanding the Glycine/Methionine-rich domain of Sis1, an Hsp40 protein, helps the propagation of VL. Over-expression of the Hsp70 protein Ssa2 lowers the number of prion particles (propagons) in the cell. There is more reduction for VK than VL, causing the latter to dominate in some of the 5V-H19 and all of the 74-D694 cells tested. Consistently, depleting Ssa1 in 74-D694 strengthens VK. Swapping chromosomal alleles of SSA1/2 and SIS1 between 5V-H19 and 74-D694, including cognate promoters, is not sufficient to change the native dominance order of each background, suggesting there exist additional polymorphic factors that modulate [PSI+ ] competition.