Meiotic recombination promotes the faithful segregation of homologous chromosomes at meiosis I (MI) by creating physical linkages between the homologs. Recombination produces two types of products: crossovers (COs) and non-crossovers (NCOs). Only COs mature into exchanges between chromosome axes called chiasmata, which together with arm cohesion ensure homolog separation.
Crossing-over during meiosis establishes the physical linkage of homologs required for their accurate segregation at the first meiotic division. Two features indicate that meiotic crossing-over is a highly regulated process. First, "crossover assurance" or the "obligatory crossover" describes the observation that each pair of homologs always obtains at least one crossover despite the fact that the average per chromosome pair is quite low (typically 1-3 crossovers). Second, adjacent crossovers are more widely spaced than random expectations, a phenomenon known as crossover interference.
Meiotic recombination is initiated by DNA double-strand breaks (DSBs) and the total number of DSBs greatly exceeds the final number of crossovers. Thus, there must be processes that designate a crossover fate to selected DSBs and then implement that fate with high efficiency. The remaining majority of DSBs is repaired as noncrossovers without exchange of chromosome arms.
At the DNA level, differentiation of crossover and noncrossover pathways can be detected at an early stage. DSBs undergo resection of the 5'-strands to yield long 3'-single-strand tails. DSB-ends then interact sequentially with a homolog to form two types joint molecule intermediate. Invasion by one DSB-end produces a Single-End Invasion (SEI). DNA synthesis and interaction of the second end then convert the SEI into a double Holliday Junction (dHJ). In theory, dHJs can be resolved into both crossover and noncrossover products but available evidence suggests dHJs give rise primarily or exclusively to crossovers. Moreover, SEIs also appear to be crossover-specific intermediates Joint molecules that are specific to the noncrossover pathway have not been identified, perhaps because they are labile and/or short-lived. It is proposed that crossover or noncrossover designation occurs very early, at or before transition from DSBs to SEIs.
Meiotic recombination also mediates homolog pairing, culminating in the formation of synaptonemal complexes (SCs), which connect homologs along their entire lengths. Meiotic homologs assemble a proteinacious core or axis. During the leptotene stage DSBs form and homolog axes pair, becoming closely associated at sites of recombination. These axial associations are thought to be sites where SC polymerization initiates during zygotene. When SCs have polymerized along the lengths of all homolog pairs, cells enter the pachytene stage. dHJs are formed and resolved into crossovers during this stage.
We are interested in molecular mechanisms and their control of chromosome morphogenesis and chromosome movement as well as recombination during meiosis
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