Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation

Simone Bertolini, Bin Wang, Bettina Meier, Ye Hong, Anton Gartner (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
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Abstract

Relatively little is known about the crosstalk between the spindle assembly checkpoint and the DNA damage response, especially in multicellular organisms. We performed a Caenorhabditis elegans forward genetic screen to uncover new genes involved in the repair of DNA damage induced by ionizing radiation. We isolated a mutation, gt2000 which confers hypersensitivity to ionizing radiation and showed that gt2000 introduces a premature stop in bub-3 BUB-3 is a key component of the spindle assembly checkpoint. We provide evidence that BUB-3 acts during development and in the germline; irradiated bub-3(gt2000) larvae are developmentally retarded and form abnormal vulvae. Moreover, bub-3(gt2000) embryos sired from irradiated worms show increased levels of lethality. Both bub-3 and san-1 (the Caenorhabditis elegans homologue of MAD3) deletion alleles confer hypersensitivity to ionizing radiation, consistent with the notion that the spindle assembly checkpoint pathway is required for DNA damage response. bub-3(gt2000) is moderately sensitive to the crosslinking drug cisplatin but not to UV light or methyl methanesulfonate. This is consistent with role in dealing with DNA double-strand breaks and not with base damage. Double mutant analysis revealed that bub-3 does not act within any of the three major pathways involved in the repair of double-strand breaks. Finally, the cdc-20 gain-of-function mutant cdc-20/fzy-1(av15), which is refractory to the cell cycle delay conferred by the spindle checkpoint showed phenotypes similar to bub-3 and san-1 mutants. We speculate that BUB-3 is involved in DNA damage response through regulation of cell cycle timing.

Original languageEnglish
Pages (from-to)3875-3885
Number of pages11
JournalG3 : Genes, Genomes, Genetics
Volume7
Issue number12
Early online date18 Oct 2017
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Ionizing radiation
  • Spindle Assembly Checkpoint
  • BUB-3, SAN-1/MAD-3
  • DNA damage response

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