RRC ID 53943
Author Hong Y, Velkova M, Silva N, Jagut M, Scheidt V, Labib K, Jantsch V, Gartner A.
Title The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans.
Journal PLoS Genet
Abstract Homologous recombination is essential for crossover (CO) formation and accurate chromosome segregation during meiosis. It is of considerable importance to work out how recombination intermediates are processed, leading to CO and non-crossover (NCO) outcome. Genetic analysis in budding yeast and Caenorhabditis elegans indicates that the processing of meiotic recombination intermediates involves a combination of nucleases and DNA repair enzymes. We previously reported that in C. elegans meiotic joint molecule resolution is mediated by two redundant pathways, conferred by the SLX-1 and MUS-81 nucleases, and by the HIM-6 Bloom helicase in conjunction with the XPF-1 endonuclease, respectively. Both pathways require the scaffold protein SLX-4. However, in the absence of all these enzymes, residual processing of meiotic recombination intermediates still occurs and CO formation is reduced but not abolished. Here we show that the LEM-3 nuclease, mutation of which by itself does not have an overt meiotic phenotype, genetically interacts with slx-1 and mus-81 mutants, the respective double mutants displaying 100% embryonic lethality. The combined loss of LEM-3 and MUS-81 leads to altered processing of recombination intermediates, a delayed disassembly of foci associated with CO designated sites, and the formation of univalents linked by SPO-11 dependent chromatin bridges (dissociated bivalents). However, LEM-3 foci do not colocalize with ZHP-3, a marker that congresses into CO designated sites. In addition, neither CO frequency nor distribution is altered in lem-3 single mutants or in combination with mus-81 or slx-4 mutations. Finally, we found persistent chromatin bridges during meiotic divisions in lem-3; slx-4 double mutants. Supported by the localization of LEM-3 between dividing meiotic nuclei, this data suggest that LEM-3 is able to process erroneous recombination intermediates that persist into the second meiotic division.
Volume 14(6)
Pages e1007453
Published 2018-6-1
DOI 10.1371/journal.pgen.1007453
PMID 29879106
PMC PMC6007928
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Chromatin / genetics Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Chromosome Segregation / genetics* Crossing Over, Genetic / genetics Endodeoxyribonucleases / genetics* Endodeoxyribonucleases / metabolism Endonucleases / genetics Endonucleases / metabolism Female Meiosis / genetics* Mutation RNA Interference RNA, Double-Stranded / metabolism Recombinational DNA Repair / genetics* Signal Transduction / genetics
IF 5.175
Times Cited 4
C.elegans tm3468