Identification of Suppressors of top-2 Embryonic Lethality in Caenorhabditis elegans

Autor: Nirajan Bhandari, Christine Rourke, Thomas Wilmoth, Alekya Bheemreddy, David Schulman, Dina Collins, Harold E. Smith, Andy Golden, Aimee Jaramillo-Lambert
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: G3: Genes, Genomes, Genetics, Vol 10, Iss 4, Pp 1183-1191 (2020)
Druh dokumentu: article
ISSN: 2160-1836
DOI: 10.1534/g3.119.400927
Popis: 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.
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