▪ Abstract Meiotic chromosomes have been studied for many years, in part because of the fundamental life processes they represent, but also because meiosis involves the formation of homolog pairs, ...

Meiotic chromosomes: integrating structure and function.

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.

Recombinational DNA double-strand breaks in mice precede synapsis

https://www.cell.com/cell/pdf/0092-8674(87)90078-X.pdf

A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion

The nature of the relationship between the two types of meiotic recombination outcomes, exchange (crossing-over) and simple gene conversion, has been debated for years. I here propose that these two types of events are not necessarily causally related and hypothesize that the primary role of events detected as simple gene conversion is in the recognition of homology during synapsis.

Gene conversion, recombination nodules, and the initiation of meiotic synapsis

Homologous chromosome synapsis and meiotic recombination are facilitated by several meiosis-specific structures: the synaptonemal complex (SC), and two types of meiotic nodules: (1) early meiotic nodules (MNs), also called zygotene nodules or early recombination nodules, and (2) late recombination nodules (RNs). The former are thought to be nucleoprotein complexes involved in the check for homology preceding, or accompanying synapsis, while the latter have been shown to be involved in reciprocal recombination. We have examined by immunocytochemistry the meiotic localization of a series of proteins at sites along the asynapsed axial elements prior to homologous synapsis and at sites along the SCs following synapsis. Several of the proteins examined have been implicated in repair/recombination and include RAD51, a mammalian homolog of the Escherichia coli RecA protein; Replication Protein-A (RPA), a single-strand DNA binding protein; and MLH1, a mismatch repair protein which is a homolog of the E. coli MutL protein. In addition two proteins were examined that have been implicated in meiotic checkpoints: ATM, the protein mutated in the human disease Ataxia Telangiectasia, and ATR, another member of the same family of PIK kinases. We present evidence that these proteins are all components of meiotic nodules and document changes in protein composition of these structures during zygonema and pachynema of meiotic prophase in mouse spermatocytes. These studies support the supposition that a subset of MNs are converted into RNs. However, our data also demonstrate changes in protein composition within the context of early MNs, suggesting a differentiation of these nodules during the process of synapsis. The same changes in protein composition occurred on both the normal X axis, which has no homologous pairing partner in spermatocytes, and on the axes of aberrant chromosomes that nonhomologously synapse during synaptic adjustment. These findings suggest that DNA sequences associated with MNs still must undergo an obligatory processing, even in the absence of interactions between homologous chromosomes.

Changes in protein composition of meiotic nodules during mammalian meiosis

Surface spread spermatocytes of mice heterozygous for a tandem duplication show nuclei in late zygotene-early pachytene in which the heteromorphic synaptonemal complex (SC) contains a lateral element that is buckled out into an unpaired loop as a consequence of the added length of the duplication (estimated in another study to be 21.7%, with breakpoints at 0.50 and 0.72 of the length of the chromosome). The ends of the buckle, marking the interstitial termini of synapsis proceeding from opposite directions, vary over a wide range of positions, but within limits: the proximal end of the loop does not exceed the distal end of the duplication segment, while the distal end of the loop does not lie closer to the kinetochore than the proximal end of the segment. Thus, synapsis (SC formation) at zygotene is restricted to homologous regions (exclusive homosynapsis). — In the last half of pachytene, no buckles are found, only simple SCs with lateral elements of equal length, as a consequence of synaptic adjustment. Intermediate stages of adjustment are found throughout the first half of pachytene. Shortly after homosynapsis is complete, synaptic adjustment begins: the ends of the duplication loop separate (desynapsis of homosynapsed regions); the long axis shortens with respect to the short axis in both the unpaired loop and in the SC portions; asymmetrical twists take up inequalities; the loop is reduced to from 1 to 3 asymmetrical twists; the axes (lateral elements) equalize as the long axis shortens; and a simple SC is formed, indistinguishable from others in the complement, in which the region of the duplication and those adjacent to it have heterosynapsed, while the distal regions of the SC are presumably still homosynapsed. Synaptic adjustment evidently involves two sequential events: localized instability of the homosynapsed condition, leading to desynapsis, then restoration of the SC by heterosynapsis. Adjustment therefore represents the loss of strict homosynapsis. It is concluded that the asymmetry produced by the duplication loop constitutes an instability that triggers synaptic adjustment.

P. A. Poorman

Papers

Synaptonemal complex analysis of mouse chromosomal rearrangements. I. Cytogenetic observations on a tandem duplication.