title: The Aspergillus nidulans sldI(RAD50) gene interacts with bimE(APC1), a homologue of an anaphase-promoting complex subunit.
abstract: The Mre11-Rad50-Nbs1 protein complex has emerged as a central component in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. We have identified Aspergillus nidulans sldI1444D mutant in a screen for dynein synthetic lethals. The sldI(RAD50) gene was cloned by complementation of the sporulation deficiency phenotype of this mutant. A transversion G-->C at the position 2509 (Ala-692-Pro amino acid change) in the sldI1444D mutant causes sensitivity to several DNA-damaging agents. The mutation sldI1 occurs at the CXXC hinge domain of Rad50. We have deleted part of the coiled-coil and few amino acids of the Rad50-Mre11 interaction region and assessed several phenotypic traits in this deletion strain. Besides sensitivity to a number of DNA-damaging agents, this deletion strain is also impaired in the DNA replication checkpoint response, and in ascospore viability. There is no delay of the S-phase when germlings of both sldI (RAD50) and mreA(MRE11) inactivation strains were exposed to the DNA damage caused by bleomycin. Transformation experiments and Southern blot analysis indicate homologous recombination is dependent on scaA(NBS1) function in the Mre11 complex. There are epistatic and synergistic interactions between sldI( RAD50) and bimE(APC1) at S-phase checkpoints and response to hydroxyurea and UV light. Our results suggest a possible novel feature of the Mre11 complex in A. nidulans, i.e. a relationship with bimE (APC1).
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Iran
authors.initials: I
authors.lastname: Malavazi
authors.forename: Joel Fernandes
authors.initials: JF
authors.lastname: Lima
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: von Zeska Kress Fagundes
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Efimov
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: de Souza Goldman
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D001761:Bleomycin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006918:Hydroxyurea / Q000494:pharmacology; D008540:Meiosis; D009154:Mutation; D021122:Protein Subunits; D011995:Recombination, Genetic; D016196:S Phase / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C577335:ANAPC1 protein, human; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; C065697:BIME protein, Emericella nidulans; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C478035:Nbs1 protein, S pombe; D021122:Protein Subunits; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D001761:Bleomycin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D006918:Hydroxyurea