title: The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis.
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.
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Remi
authors.initials: R
authors.lastname: Sonneville
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Agostinho
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Bettina
authors.initials: B
authors.lastname: Meier
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: J Julian
authors.initials: JJ
authors.lastname: Blow
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
authors.forename: Anton
authors.initials: A
authors.lastname: Gartner
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: C528463:BRC-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C487047:HIM-6 protein, C elegans; D046912:Multiprotein Complexes; C000594909:SMC-5 protein, C elegans; C000594910:SMC-6 protein, C elegans