RRC ID 51507
Author Bertolini S, Wang B, Meier B, Hong Y, Gartner A.
Title Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation.
Journal G3 (Bethesda)
Abstract Relatively little is known about the cross-talk 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 C. elegans homolog of MAD3) deletion alleles confer hypersensitivity to ionizing radiation, consistent with the notion that the spindle assembly checkpoint pathway is required for the DNA damage response. bub-3(gt2000) is moderately sensitive to the cross-linking drug cisplatin but not to ultraviolet light or methyl methanesulfonate. This is consistent with a 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 the DNA damage response through regulation of cell cycle timing.
Volume 7(12)
Pages 3875-3885
Published 2017-12-4
DOI 10.1534/g3.117.1122
PII g3.117.1122
PMID 29046436
PMC PMC5714485
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Caenorhabditis elegans Proteins / radiation effects Cdc20 Proteins / genetics* Cell Cycle Proteins / genetics* Cell Cycle Proteins / physiology Cell Cycle Proteins / radiation effects DNA Breaks, Double-Stranded DNA Damage / genetics DNA Damage / radiation effects Gene Expression Regulation / radiation effects Genomic Instability / genetics Genomic Instability / radiation effects M Phase Cell Cycle Checkpoints / genetics* M Phase Cell Cycle Checkpoints / radiation effects Mutation Radiation, Ionizing
IF 2.781
Times Cited 1
C.elegans tm1145 tm2026 tm2842 tm2940