Identification of Suppressors of top-2 Embryonic Lethality in Caenorhabditis elegans.
Topoisomerase II is an enzyme with important roles in chromosome biology. This enzyme relieves supercoiling and DNA and RNA entanglements generated during mitosis. Recent studies have demonstrated that Topoisomerase II is also involved in the segregation of homologous chromosomes during the first meiotic division. However, the function and regulation of Topoisomerase II in meiosis has not been fully elucidated. Here, we conducted a genetic suppressor screen in Caenorhabditis elegans to identify putative genes that interact with topoisomerase II during meiosis. Using a temperature-sensitive allele of topoisomerase II, top-2 ( it7ts ), we identified eleven suppressors of top-2-induced embryonic lethality. We used whole-genome sequencing and a combination of RNAi and CRISPR/Cas9 genome editing to identify and validate the responsible suppressor mutations. We found both recessive and dominant suppressing mutations that include one intragenic and 10 extragenic loci. The extragenic suppressors consist of a known Topoisomerase II-interacting protein and two novel interactors. We anticipate that further analysis of these suppressing mutations will provide new insights into the function of Topoisomerase II during meiosis.
['Bhandari|Nirajan|N|', 'Rourke|Christine|C|0000-0002-4585-657X', 'Wilmoth|Thomas|T|', 'Bheemreddy|Alekya|A|', 'Schulman|David|D|', 'Collins|Dina|D|', 'Smith|Harold E|HE|', 'Golden|Andy|A|', 'Jaramillo-Lambert|Aimee|A|0000-0001-7697-8580']
D000483:Alleles D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D008540:Meiosis D008938:Mitosis
top-2 topoisomerase II meiosis C. elegans