Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae.
Photoactivated psoralens used in treatment of skin diseases like Psoriasis and Vitiligo cause DNA damage, the repair of which may lead to mutations and thus to higher risk to have skin cancer. The simple eukaryote Saccharomyces cerevisiae was chosen to investigate the cells' genetic endowment with repair mechanisms for this type of DNA damage and to study the genetic consequences of such repair. Genetic studies on yeast mutants sensitive to photoactivated psoralens, named pso mutants, showed their allocation to 10 distinct loci. Cloning and molecular characterization allowed their grouping into three functional classes: (I) the largest group comprises seven PSO genes that are either generally or specifically involved in error-prone DNA repair and thus affect induced mutability and recombination; (II) one PSO gene that represents error-free excision repair, and (III) two PSO genes encoding proteins not influencing DNA repair but physiological processes unrelated to nucleic acid metabolism. Of the seven DNA repair genes involved in induced mutagenesis three PSO loci [PSO1/REV3, PSO8/RAD6, PSO9/MEC3] were allelic to already known repair genes, whereas three, PSO2/SNM1, PSO3/RNR4, and PSO4/PRP19 represent new genes involved in DNA repair and nucleic acid metabolism in S. cerevisiae. Gene PSO2 encodes a protein indispensable for repair of interstrand cross-link (ICL) that are produced in DNA by a variety of bi- and polyfunctional mutagens and that appears to be important for a likewise repair function in humans as well. In silico analysis predicts a putative endonucleolytic activity for Pso2p/Snm1p in removing hairpins generated as repair intermediates. The absence of induced mutation in pso3/rnr4 mutants indicates an important role of this subunit of ribonucleotide reductase (RNR) in regulation of translesion polymerase zeta in error-prone repair. Prp19p/Pso4p influences efficiency of DNA repair via splicing of pre-mRNAs of intron-containing repair genes but also may function in the stability of the nuclear scaffold that might influence DNA repair capacity. The seventh gene, PSO10 which controls an unknown step in induced mutagenesis is not yet cloned. Two genes, PSO6/ERG3 and PSO7/COX11, are responsible for structural elements of the membrane and for a functional respiratory chain (RC), respectively, and their function thus indirectly influences sensitivity to photoactivated psoralens.
Brendel
Martin
M
Departamento de Biofisica, Centro de Biotecnologia, UFRGS, Av. Bento Gonçalves 9500, 91507-970 Porto Alegre, RS, Brazil.
Bonatto
Diego
D
Strauss
Martin
M
Revers
Luis Fernando
LF
Pungartnik
Cristina
C
Saffi
Jenifer
J
Henriques
João Antonio Pegas
JA
D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004271:DNA, Fungal / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000528:radiation effects; D009153:Mutagens / Q000493:pharmacokinetics; D009713:Nucleotidyltransferases / Q000235:genetics* / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000528:radiation effects; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase; D009153:Mutagens; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; C471606:RAD6 protein, S cerevisiae; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases; C092602:REV3 protein, S cerevisiae