In vivo levels of S-adenosylmethionine modulate C:G to T:A mutations associated with repeat-induced point mutation in Neurospora crassa.
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.
Rosa
Alberto Luis
AL
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Friuli 2434, Col. Velez Sarsfield, 5016 Córdoba, Argentina. arosa@wsu.edu
Folco
Hernán Diego
HD
Mautino
Mario Ricardo
MR
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
D004271:DNA, Fungal; D011993:Recombinant Fusion Proteins; D012436:S-Adenosylmethionine; D008716:Methionine Adenosyltransferase