Abstract
Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis.
Highlights
Homologous recombination (HR) accurately repairs DNA double-strand breaks (DSBs)
Meiosis is a special form of cell division needed for the formation of haploid gametes
In this study we show that the concerted action of the Bloom syndrome helicase (BLM) helicase HIM-6 and the evolutionarily conserved structural maintenance of chromosome (SMC)-5/6 complex are important for the ordered processing of meiotic recombination intermediates, proper crossover (CO) formation and subsequent chromosome segregation in C. elegans
Summary
Homologous recombination (HR) accurately repairs DNA double-strand breaks (DSBs). DSBs are resected to create long single-strand DNA tails, which can invade intact homologous donor sequences with the aid of the conserved Rad recombinase. The invading strand primes DNA synthesis using the intact homologous chromosomes as a template and second-end DNA capture leads to formation of cruciform recombination intermediates known as Holliday junctions (HJs). The sister chromatids are preferentially used as repair templates, thereby preventing potentially deleterious effects of recombination, such as loss of heterozygosity. COs are important for the exchange of genetic information between maternal and paternal chromosomes, but together with sister chromatid cohesion they provide a transient physical linkage between homologs (chiasmata) that prevents precocious chromosomes segregation before the end of meiosis I
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