RRC ID 22015
著者 Li X, Zhuo R, Tiong S, Di Cara F, King-Jones K, Hughes SC, Campbell SD, Wevrick R.
タイトル The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in Drosophila melanogaster.
ジャーナル PLoS One
Abstract The SMC5/6 protein complex consists of the Smc5, Smc6 and Non-Smc-Element (Nse) proteins and is important for genome stability in many species. To identify novel components in the DNA repair pathway, we carried out a genetic screen to identify mutations that confer reduced resistance to the genotoxic effects of caffeine, which inhibits the ATM and ATR DNA damage response proteins. This approach identified inactivating mutations in CG5524 and MAGE, homologs of genes encoding Smc6 and Nse3 in yeasts. The fact that Smc5 mutants are also caffeine-sensitive and that Mage physically interacts with Drosophila homologs of Nse proteins suggests that the structure of the Smc5/6 complex is conserved in Drosophila. Although Smc5/6 proteins are required for viability in S. cerevisiae, they are not essential under normal circumstances in Drosophila. However, flies carrying mutations in Smc5, Smc6 and MAGE are hypersensitive to genotoxic agents such as ionizing radiation, camptothecin, hydroxyurea and MMS, consistent with the Smc5/6 complex serving a conserved role in genome stability. We also show that mutant flies are not compromised for pre-mitotic cell cycle checkpoint responses. Rather, caffeine-induced apoptosis in these mutants is exacerbated by inhibition of ATM or ATR checkpoint kinases but suppressed by Rad51 depletion, suggesting a functional interaction involving homologous DNA repair pathways that deserves further scrutiny. Our insights into the SMC5/6 complex provide new challenges for understanding the role of this enigmatic chromatin factor in multi-cellular organisms.
巻・号 8(3)
ページ e59866
公開日 2013-3-28
DOI 10.1371/journal.pone.0059866
PII PONE-D-13-00199
PMID 23555814
PMC PMC3610895
MeSH Alleles Animals Apoptosis Caffeine / pharmacology* Cell Cycle Proteins / physiology* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / physiology* Chromosome Mapping / methods Crosses, Genetic DNA Damage* DNA Repair Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / genetics Drosophila melanogaster / physiology* Ethyl Methanesulfonate / pharmacology Eye / pathology Homozygote Models, Genetic Mutation Nerve Tissue Proteins / genetics Nerve Tissue Proteins / physiology* Phenotype Protein Binding
IF 2.74
引用数 12
リソース情報
ショウジョウバエ NP2592 (DGRC#104251) GS3245 (DGRC#200582) GS14577 (DGRC#205862)