Excess crossovers impede faithful meiotic chromosome segregation in C. elegans

Abstract

During meiosis, diploid organisms reduce their chromosome number by half to generate haploid gametes. This process depends on the repair of double strand DNA breaks as crossover recombination events between homologous chromosomes, which hold homologs together to ensure their proper segregation to opposite spindle poles during the first meiotic division. Although most organisms are limited in the number of crossovers between homologs by a phenomenon called crossover interference, the consequences of excess interfering crossovers on meiotic chromosome segregation are not well known. Here we show that extra interfering crossovers lead to a range of meiotic defects and we uncover mechanisms that counteract these errors. Using chromosomes that exhibit a high frequency of supernumerary crossovers in Caenorhabditis elegans, we find that essential chromosomal structures are mispatterned in the presence of multiple crossovers, subjecting chromosomes to improper spindle forces and leading to defects in metaphase alignment. Additionally, the chromosomes with extra interfering crossovers often exhibited segregation defects in anaphase I, with a high incidence of chromatin bridges that sometimes created a tether between the chromosome and the first polar body. However, these anaphase I bridges were often able to resolve in a LEM-3 nuclease dependent manner, and chromosome tethers that persisted were frequently resolved during Meiosis II by a second mechanism that preferentially segregates the tethered sister chromatid into the polar body. Altogether these findings demonstrate that excess interfering crossovers can severely impact chromosome patterning and segregation, highlighting the importance of limiting the number of recombination events between homologous chromosomes for the proper execution of meiosis.

A degron-based strategy reveals new insights into Aurora B function in C. elegans

“…For instance, AIR-2 and other CPC components are often mispatterned in the absence of AIR-2 kinase activity ( Fig 1 and S3 Fig ), so these chromosome structure defects could cause the failure to assemble the RC. However, bivalents containing multiple chiasmata have major CPC patterning defects but can still assemble RC components, demonstrating that proper chromosome structure is not a pre-requisite for RC assembly [ 17 ]. Similarly, it is possible that failure to assemble the RC in the AIR-2 KD TG strain causes the later spindle assembly and chromosome segregation defects.…”

“…AIR-2 is also essential for the assembly of the "ring complex" (RC), which encircles the center of each bivalent during Meiosis I (and the sister-chromatid interface during Meiosis II) [13][14][15][16]. The CPC is required for localization of all other known RC components [14,15], and chromosomes lacking RCs or with improperly patterned RCs show defects in chromosome congression [13,17]. Finally, AIR-2 depletion has been reported to cause spindle defects in C. elegans oocytes [6,8,14,15], although what part of the spindle assembly pathway is affected has not been investigated.…”

Meiotic Crossover Patterning

“…A study in C. elegans found that interference plays a key role in ensuring proper chromosome segregation by limiting the number of crossovers per homolog (Hollis et al, 2020); however, this may be a problem unique to organisms without defined centromeres. Interference may serve to limit the number of crossovers, but in Arabidopsis, increasing crossovers by three-sixfold has no apparent negative effect on fertility or chromosome segregation (Crismani et al, 2012;Girard et al, 2015).…”

Analysis of meiosis in Pristionchus pacificus reveals plasticity in homolog pairing and synapsis in the nematode lineage

“…Thus, this particular solution to the problem of segregating holocentric chromosomes in meiosis appears to predate the Rhabditine radiation. This pathway relies on the formation of two bivalent "arms" with reciprocal functions, which in turn depends on strict crossover interference; multiple crossovers "confuse" the system and lead to frequent missegregation (Hollis et al, 2020). We expect that these two features of meiosis are widely shared among and perhaps beyond Clade V nematodes.…”