Caenorhabditis elegans HIM-18/SLX-4 interacts with SLX-1 and XPF-1 and maintains genomic integrity in the germline by processing recombination intermediates.
Homologous recombination (HR) is essential for the repair of blocked or collapsed replication forks and for the production of crossovers between homologs that promote accurate meiotic chromosome segregation. Here, we identify HIM-18, an ortholog of MUS312/Slx4, as a critical player required in vivo for processing late HR intermediates in Caenorhabditis elegans. DNA damage sensitivity and an accumulation of HR intermediates (RAD-51 foci) during premeiotic entry suggest that HIM-18 is required for HR-mediated repair at stalled replication forks. A reduction in crossover recombination frequencies-accompanied by an increase in HR intermediates during meiosis, germ cell apoptosis, unstable bivalent attachments, and subsequent chromosome nondisjunction-support a role for HIM-18 in converting HR intermediates into crossover products. Such a role is suggested by physical interaction of HIM-18 with the nucleases SLX-1 and XPF-1 and by the synthetic lethality of him-18 with him-6, the C. elegans BLM homolog. We propose that HIM-18 facilitates processing of HR intermediates resulting from replication fork collapse and programmed meiotic DSBs in the C. elegans germline.
Saito
Takamune T
TT
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Youds
Jillian L
JL
Boulton
Simon J
SJ
Colaiácovo
Monica P
MP
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics; D002875:Chromosomes / Q000378:metabolism; D017124:Conserved Sequence; D003434:Crossing Over, Genetic; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D045566:DNA, Cruciform / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism; D016678:Genome / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism*; D008540:Meiosis; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011418:Prophase; D011485:Protein Binding; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D000099257:Meiotic Recombination Protein SPO11
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004265:DNA Helicases; D045566:DNA, Cruciform; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D004950:Esterases; D000099257:Meiotic Recombination Protein SPO11; C575962:HIM-18 protein, C elegans; C547401:SLX-1 protein, C elegans; C547402:XPF-1 protein, C elegans