Mutation Research 489 (2001) 79–96 Review The pso mutants of Saccharomyces cerevisiae comprise two groups: one deficient in DNA repair and another with altered mutagen metabolism Martin Brendel a , João Antonio P. Henriques b,∗ a Institut für Mikrobiologie, J.W. Goethe-Universität, 60596 Frankfurt, Main, Germany b Department of Biophysics, Biotechnology Center, UFRGS, Av. Bento Gonçalves 9.500, 91507-970 Porto Alegre, RS, Brazil Received 2 April 2001; received in revised form 24 July 2001; accepted 24 July 2001 Abstract Yeast mutants that are sensitive to photoactivated psoralens, named pso mutants, were isolated and described more than 20 years ago. Nine genes responsible for the pso phenotypes were identified and seven of them cloned and molecularly characterized. Of the nine PSO genes of yeast seven apparently encode proteins involved in the repair of DNA lesions generated by photoinduced psoralens and by other mutagens, while two, PSO6 and PSO7, are responsible for structural elements of the membrane and for a functional respiratory chain, respectively. Of the seven proven or putative DNA repair genes six directly or indirectly control induced mutagenesis. Four of these PSO loci were found allelic to already known repair genes, whereas two, PSO2 and PSO4, represent new genes involved in DNA repair and in repair/pre-mRNA processing in S. cerevisiae. Gene PSO2 encodes a protein indispensable for repair of DNA interstrand cross-links that are produced by a variety of bi- and poly-functional mutagens and that appears to be important for a likewise repair function in humans as well. © 2001 Published by Elsevier Science B.V. Keywords: Yeast; Psoralen sensitivity; DNA repair; Mutagenesis; Cross-link repair; Pre-mRNA splicing; Ergosterol; Cytochrome c oxidase 1. Introduction Phototherapy with UVB alone or with UVA-activated Psoralen (PUVA) has been developed many years ago in order to treat dermatological disorders rang- ing from atopic dermatitis to psoriasis and vitiligo ————– Abbreviations: BER, base excision repair; cis-, transDDP, cis- and transPlatin, respectively; DEO, diepoxyoctane; DSB, DNA double-strand breaks; 8HQ, 8-hydroxyquinolineoxide; 8-MOP + UVA, 3-CPs + UVA, pre-treatment with 8-methoxypsoralen, respectively, 3-carbethoxy- psoralen and irradiation with 365 nm UV-light; 4NQO, 4-nitroquinoline N-oxide; HN1, nitrogen half mustard; HN2, nitrogen mustard; ICL, interstrand cross-link; MNNG, N-methyl-N ′ -nitro-N-nitrosoguanidine; NDEA, N-nitrosodiethylamine; NER, nucleotide excision repair; TLS, translesion synthesis; UVC, irradiation with 254 nm UV-light; WT, wild type ∗ Corresponding author. Tel.: +55-51-3316-6087; fax: +55-51-3319-1079. E-mail addresses: brendel@em.uni-frankfurt.de (M. Brendel), pegas@dna.cbiot.ufrgs.br (J.A.P. Henriques). [1]. Photoactivated psoralens may react with proteins and nucleic acids and when PUVA phototherapy was shown to induce DNA lesions [2], it became clear that this might result in induced mutation and an elevated risk for skin cancer [3]. Depending on the type of pso- ralen used (mono- or bi-functional) the UVA-activated 1383-5742/01/$ – see front matter © 2001 Published by Elsevier Science B.V. PII:S1383-5742(01)00066-7