Meiosis

Abstract

Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In C. elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes; the changes in chromosome structure that chromosomes undergo during meiosis; the events of meiotic recombination; the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I; and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans

“…We analysis, we discovered defects in 39% of diakinetic oocytes examined ( Figure 6C). These data are consistent with our findings that Mi2 deficiency results in persisting recombination intermediates and chromosomal fusions, a hallmark of spurious repair of meiotic DSBs via NHEJ (Figures 4-5; Hillers, 2017). Further, these findings indicate that defective let-418 nuclei that bypass the recombination checkpoint directly contribute to fertility defects, which we speculate is at least in part due to aberrant engagement of NHEJ (Figure 7).…”

“…As expected, univalents appeared structurally normal in syp-3 single mutants, yet several for Mi2 involvement in non-crossover pathways, which when defective, can activate alternative repair routes such as NHEJ and manifest in this phenotype (Hillers, 2017;Shrivastav et al, 2008). chromatin landscape conducive to DNA repair (Lans et al, 2012).…”

“…In C. elegans, these types of structural defects can be detected in late prophase nuclei as either additional DAPI-staining bodies, chromosomal fusions, or fragmented DNA (Hillers, 2017). As in wild-type worms, nearly all chd-3 and let-418 mutants possessed six intact DAPI-staining bodies in diakinesis (DI) stage oocytes, corresponding to six paired homologs ( Figure 5A-B).…”

“…To date, no studies have investigated the contributions of NuRD during meiosis, and we therefore asked whether Mi2 plays a role in the regulation of meiotic DSBs. To test this, we took advantage of the unique spatio-temporal organization of the C. elegans gonad, which allows for cytological analysis of the formation and repair of DSBs (Hillers, 2017;Lui and Colaiácovo, 2013; Figure 4A). To determine whether loss of either Mi2 subunit manifests in defective DSB repair, we monitored the kinetics of the recombinase RAD-51 in wild-type, let-418(n3536) hypomorphs and chd-3(eh4) null mutants, singly and in combination ( Figure 4B-F Figure S4).…”

“…In contrast, structural defects were seen in 33% of chd-3(RNAi);let-418 diakinetic nuclei, the majority of which contained four or five DAPI-staining structures, indicative of chromosome fusions ( Figure 5A-B). Fusions are elicited in response to defective DSB repair and can result from either spurious activation of error-prone repair or telomerase deficiency (Hillers, 2017;Lowden et al, 2011;Wong et al, 2000). As either scenario would be consistent with elevated checkpoints and increased genomic instability, we conclude that the presence of Mi2 is required for promoting HR and the prevention of gross chromosomal abnormalities that would compromise fertility, as evidenced by the significant reduction in viable gametes in chd-3(RNAi);let-418 mutants (Figure 3).…”