title: DNA topoisomerase 2 mutant allele mildly delays the mitotic progression and activates the checkpoint protein kinase Chk1 in fission yeast Schizosaccharomyces pombe.
abstract: DNA topoisomerases are specialized nuclear enzymes that perform topological modifications on double-stranded DNA (dsDNA) and hence are essential for DNA metabolism such as replication, transcription, recombination, condensation and segregation. In a genetic screen, we identified a temperature-sensitive mutant allele of topoisomerase 2 that exhibits conditional synthetic lethality with a chk1 knockout strain. The mutant allele of topoisomerase 2 is defective in chromosome segregation at a non-permissive temperature and there was increase in chromosome segregation defects in the double mutant of top2-10 and chk1 delete at a non-permissive temperature. More importantly, topoisomearse 2 mutant cells mildly delay the mitotic progression at non-permissive temperature that is mediated by checkpoint protein kinase Chk1. Additionally, top2-10 mutant cells also activate the Chk1 at a non-permissive temperature and this activation of Chk1 takes place at the time of mitosis. Interestingly, top2-10 mutant cells retain their viability at a non-permissive temperature if the cells are not allowed to enter into mitosis. Taking together our results, we speculate that in the top2-10 mutant, the segregation of entangled chromatids during mitosis could result in delaying the mitotic progression through the activation of Chk1 kinase.
authors.affiliation: Molecular and Structural Biology Division, Central Drug Research Institute, CSIR Chattar Manzil Palace, MG Road, Lucknow 226001, India.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Yadav
authors.forename: Sumit Kumar
authors.initials: SK
authors.lastname: Verma
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D002842:Chromatids / Q000235:genetics; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics; D004249:DNA Damage; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D005804:Genes, Lethal; D008938:Mitosis / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D004250:DNA Topoisomerases, Type II