caenorhabditis elegans him-18slx-4 interacts with slx-1 and xpf-1 and maintains genomic integrity in the germline by processing recombination intermediates秀丽隐杆线虫him-18slx-4与slx-1 xpf-1和维持基因组完整性的生殖系处理复合中间体.pdfVIP

Caenorhabditis elegans HIM-18/SLX-4 Interacts with SLX-1 and XPF-1 and Maintains Genomic Integrity in the Germline by Processing Recombination Intermediates 1 2 2 ´ 1 Takamune T. Saito , Jillian L. Youds , Simon J. Boulton , Monica P. Colaiacovo * 1 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 2 DNA Damage Response Laboratory, Cancer Research UK, South Mimms, United Kingdom Abstract 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. ´ Citation: Saito TT, Youds JL, Boulton