Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division

Abstract

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...

Interactions between Mei4, Rec114, and other proteins required for meiotic DNA double-strand break formation in Saccharomyces cerevisiae

“…Mei4 and Rec114 remained bound to chromatin past the time of DSB formation (this study and Li et al 2006), a pattern that has also been observed for S. cerevisiae Spo11, Rec102, Rec104, Mer2, and Ski8 Kee et al 2004;Prieler et al 2005;Henderson et al 2006;Li et al 2006), and has been described for Ski8 and/or Spo11 in other organisms as well (Romanienko and Camerini-Otero 2000;Storlazzi et al 2003;Tessé et al 2003). It is not yet clear whether this persistence reflects additional functions after DSB formation.…”

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

“…However, mutants of Sordaria macrospora and S. pombe that lack Rec12 (Spo11) have clear defects at later stages of meiosis, including reduced ability to properly separate sister chromatids at anaphase of meiosis II (Sharif et al, 2002;Storlazzi et al, 2003). These phenotypes could be an indirect, secondary consequence of loss of recombination.…”

Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes

“…Also, in Sordaria Spo11 mutants, the bouquet stage persists longer than in wild-type cells. Therefore, it has been proposed that the exit from the bouquet is mediated by a regulatory process that senses the progression of a recombination-related process (Storlazzi et al 2003). In contrast, bouquet arrest in Rad21L knockout spermatocytes is not suppressed by Spo11 knockout in mice (Fig.…”

“…After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http:// creativecommons.org/licenses/by-nc/4.0/. DSB-dependent recombination and subsequent synapsis, DSB-independent mechanisms seem to promote the juxtaposition of homologs (Weiner and Kleckner 1994;Peoples et al 2002;Storlazzi et al 2003;Bhuiyan and Schmekel 2004;Ding et al 2004;Peoples-Holst and Burgess 2005). A recent study in mice reported that a DSB-independent mechanism promotes homolog pairing during premeiotic S phase prior to DSB formation (Boateng et al 2013).…”