Chromosomal processes related to formation and function of meiotic chiasmata have been analyzed in Sordaria macrospora. Double-strand breaks (DSBs), programmed or ␥-rays-induced, are found to promote four major events beyond recombination and accompanying synaptonemal complex formation: (1) juxtaposition of homologs from long-distance interactions to close presynaptic coalignment at mid-leptotene; (2) structural destabilization of chromosomes at leptotene/zygotene, including sister axis separation and fracturing, as revealed in a mutant altered in the conserved, axis-associated cohesin-related protein Spo76/Pds5p; (3) exit from the bouquet stage, with accompanying global chromosome movements, at zygotene/pachytene (bouquet stage exit is further found to be a cell-wide regulatory transition and DSB transesterase Spo11p is suggested to have a new noncatalytic role in this transition); (4) normal occurrence of both meiotic divisions, including normal sister separation. Functional interactions between DSBs and the spo76-1 mutation suggest that Spo76/Pds5p opposes local destabilization of axes at developing chiasma sites and raise the possibility of a regulatory mechanism that directly monitors the presence of chiasmata at metaphase I. Local chromosome remodeling at DSB sites appears to trigger an entire cascade of chromosome movements, morphogenetic changes, and regulatory effects that are superimposed upon a foundation of DSB-independent processes. The central unique event of meiosis, reductional segregation of homologs at division I, is mediated by chiasmata. These observable connections between homologs correspond to sites of crossing over at the DNA level and arise during meiotic prophase via a complex series of chromosomal and nuclear changes that extend well beyond the process of DNA recombination and are both intricate and poorly understood.Recombination involves a series of local biochemical changes that begin with programmed double-strand breaks (DSBs) at early prophase and occupy most of prophase (review in Keeney 2001). Formation of chiasmata requires two other types of local changes (e.g., Blat et al. 2002). First, crossing over must occur not only within the DNA, but also between the underlying chromatid axes at corresponding positions. Second, because only one chromatid of each replicated homolog is involved, sister chromatids must be differentiated and separated locally at both the DNA and axis levels. The recombination complexes seen associated with their underlying chromatid axes during early prophase (e.g., Moens et al. 2002) likely mediate spatial, temporal, and functional linkage between events at the DNA and axis levels along the chiasma formation pathway.This progression of local changes occurs in close temporal coordination with a series of global changes in chromosome structure. One obvious meiotic structural feature is the synaptonemal complex (SC), a closepacked array of transverse filaments that links homolog axes at a distance of 100 nm all along their lengths. The SC appears, persists, a...

Spo76p is conserved and related to the fungal proteins Pds5p and BIMD and the human AS3 prostate proliferative shutoff-associated protein. Spo76p localizes to mitotic and meiotic chromosomes, except at metaphase(s) and anaphase(s). During meiotic prophase, Spo76p assembles into strong lines in correlation with axial element formation. As inferred from spo76-1 mutant phenotypes, Spo76p is required for sister chromatid cohesiveness, chromosome axis morphogenesis, and chromatin condensation during critical transitions at mitotic prometaphase and meiotic midprophase. Spo76p is also required for meiotic interhomolog recombination, likely at postinitiation stage(s). We propose that a disruptive force coordinately promotes chromosomal axial compaction and destabilization of sister connections and that Spo76p restrains and channels the effects of this force into appropriate morphogenetic mitotic and meiotic outcomes.

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