title: In vivo levels of S-adenosylmethionine modulate C:G to T:A mutations associated with repeat-induced point mutation in Neurospora crassa.
abstract: In Neurospora crassa, the mutagenic process termed repeat-induced point mutation (RIP) inactivates duplicated DNA sequences during the sexual cycle by the introduction of C:G to T:A transition mutations. In this work, we have used a collection of N. crassa strains exhibiting a wide range of cellular levels of S-adenosylmethionine (AdoMet), the universal donor of methyl groups, to explore whether frequencies of RIP are dependent on the cellular levels of this metabolite. Mutant strains met-7 and eth-1 carry mutations in genes of the AdoMet pathway and have low levels of AdoMet. Wild type strains with high levels of AdoMet were constructed by introducing a chimeric transgene of the AdoMet synthetase (AdoMet-S) gene fused to the constitutive promoter trpC from Aspergillus nidulans. Crosses of these strains against tester duplications of the pan-2 and am genes showed that frequencies of RIP, as well as the total number of C:G to T:A transition mutations found in randomly selected am(RIP) alleles, are inversely correlated to the cellular level of AdoMet. These results indicate that AdoMet modulates the biochemical pathway leading to RIP.
authors.affiliation: Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Friuli 2434, Col. Velez Sarsfield, 5016 Córdoba, Argentina. arosa@wsu.edu
authors.forename: Alberto Luis
authors.initials: AL
authors.lastname: Rosa
authors.forename: Hernán Diego
authors.initials: HD
authors.lastname: Folco
authors.forename: Mario Ricardo
authors.initials: MR
authors.lastname: Mautino
mesh_terms: D000483:Alleles; D001233:Aspergillus nidulans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D003433:Crosses, Genetic; D004271:DNA, Fungal / Q000378:metabolism*; D005800:Genes, Fungal; D008716:Methionine Adenosyltransferase / Q000235:genetics*; D009492:Neurospora crassa / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000502:physiology*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D019076:Transgenes
chemical_list: D004271:DNA, Fungal; D011993:Recombinant Fusion Proteins; D012436:S-Adenosylmethionine; D008716:Methionine Adenosyltransferase