Ph.D. Cornell University (1979)
Office: Remsen 120
Phone: (718) 997-4195
FAX: 997-5531
E-mail: Wilma.Saffran@qc.cuny.edu
Research Interests: Biochemistry - Studies of DNA damage in yeast; roles of individual genes in DNA repair, mutation and recomdination; replication and transcription in recombinatorial repair.
Cellular DNA must remain intact in order to carry out its essential functions of transcription and replication, but it is subject to radiation and chemical attacks which alter its structure. All cells contain repair systems which recognize and remove DNA damage; there are both enzymes with narrow specificities which repair only one form of damage and less specific systems which act on a wide range of lesions.
Most DNA repair systems take advantage of the complementary nature of DNA strands within the duplex, replacing the missing sequence of the damaged strand by copying the intact strand. Double strand damage, producing simultaneous loss of genetic information from both strands, is more difficult to repair in an error-free manner. Repair can be accomplished by recombination, the exchange or transfer of genetic information between DNA molecules. In general, the undamaged copy donates information to the damaged copy, but transfer in the opposite direction also occurs.
Psoralen is a natural product, found in umbelliferous plants, which photoreacts with DNA to form monoadducts on single strands as well as interstrand crosslinks; one crosslink, if left unrepaired, is lethal to cells. Psoralen photoreaction causes mutations and chromosomal aberrations, and induces genetic recombination. Psoralen plus ultraviolet A (PUVA) therapy is used to treat psoriasis and other skin disorders, but has been found to be carcinogenic in humans.
We are studying the repair of double strand damage in baker's yeast, Saccharomyces cerevisiae. This organism has three major groups of DNA repair genes, carrying out excision, recombination and mutagenic repair; gene functions from all three groups are required for the repair of psoralen damage. We are characterizing the repair products of single strand damage, such as psoralen monoadducts and far UV photoproducts, and of double strand damage, such as psoralen crosslinks and double strand breaks, in strains deficient in one or more of these genes in order to define their roles. In addition, we are using DNA molecules carrying site-specifically placed psoralen adducts to map the genetic changes produced by repair in finer detail.
There are connections between DNA repair and transcription; the transcribed strand of an active gene is more quickly repaired than either the non-transcribed strand or inactive DNA, and several of the excision repair gene products are required for transcription by RNA polymerase II. Recombination is also affected by transcription, as certain forms of spontaneous recombination products are increased by transcriptional activity. We are studying the effects of transcriptional activity on recombinational repair by characterizing its effects on the frequency and types of damage-induced recombination in a transcriptionally regulated gene.
Publications:
Saffran, Wilma A., Charles R. Cantor, Elsworth D. Smith, and Magi Magdi (1992) DNA damage-induced plasmid recombination in Saccharomyces cerevisiae: dependence on RAD1 and RAD52. Mutat. Res. 274: 1-9.
Han, Eun-Kyoung, and Wilma A. Saffran (1992) Differential repair and recombination of psoralen damaged plasmid DNA in Saccharomyces cerevisiae. Mol. Gen. Genet. 236: 8- 16.
Saffran, Wilma A., Ross B. Greenberg, Mindy S. Thaler-Scheer, and Monica M. Jones (1994) Single strand and double strand DNA damage-induced reciprocal recombination in yeast. Dependence on nucleotide excision repair and RAD1 recombination. Nucl. Acids Res. 22: 2823-2829.
Last Modified September 25, 1996