Nairn, Rodney S.

Nairn, Rodney S. Ph.D.

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Research Interests

DNA repair, genetic recombination, sunlight carcinogenesis

Current Research

Sunlight carcinogenesis is an important area of cancer research, particularly in view of the recent alarming increase in malignant melanoma and other skin cancers. The incidence of malignant melanoma is rapidly increasing worldwide, accounting for approximately 3% of all cancers diagnosed yearly in the United States. In the United States and Canada, the incidence of melanoma has increased 5%-7% yearly over the past 10 years, doubling the population risk every 10-15 years. DNA repair, as well as other mechanisms of cellular homeostasis, are of central importance in the repair of UV light-induced DNA damage, which, if unrepaired or misrepaired, can lead directly to malignant changes in cells. In my laboratory, we are using two very different experimental models to study the role of UV damage and defective homeostasis processes (DNA repair and cell cycle control) in sunlight carcinogenesis. In Chinese hamster ovary (CHO) cells, we have developed isogenic mammalian cell lines harboring different DNA repair gene mutations, focusing on genes with dual functions in DNA repair and recombination. In our current studies, we are investigating how genetic recombination pathways are changed in CHO DNA repair mutants with mutations in the ERCC1, XPF, MSH3 and RAD51 paralogous genes using techniques of somatic cell and molecular genetics. These repair genes are involved in the repair of DNA interstrand crosslinks as well as other types of complex DNA damage. Because it is recognized that critical genes involved in carcinogenesis are often altered through genetic recombination, these studies address important questions concerning how DNA damage and damage processing by specific genes may lead directly to heritable alterations in cells, which can result in malignant transformation and cancer.

We have also completed work in another project involving the investigation of mechanisms of sunlight carcinogenesis using a biological model for melanoma in the fish genus Xiphophorus, comprising platyfish and swordtail species. Genetic hybrids between certain platyfish and swordtail species exhibit a high incidence of spontaneous melanoma formation, which follows simple genetic predictions. We have studied a platyfish-swordtail genetic cross in which exposure to UV light is necessary for melanomas to form, and we have cloned and genetically mapped oncogenes, DNA repair genes, and tumor suppressor genes (e.g., p53, CDKN2, Rb) from this organism in order to investigate their roles in carcinogenesis. We have shown that inheritance of one form of the fish CDKN2 gene is significantly associated with susceptibility to melanomas in the Xiphophorus model. The Xiphophorus CDKN2AB gene, which we have cloned and mapped, is structurally related, and probably ancestral, to human cell cycle-regulating genes CDKN2A and CDKN2B, which encode the p16 and p15 proteins which have been implicated as a tumor susceptibility genes in human cancers.

Recently, we have developed CHO cell culture models in which the WRN RecQ helicase is depleted (by shRNA). WRN is involved in maintaining genomic integrity through participation in pathways of DNA repair, replication, recombination and telomere maintenance. These cell lines are being used in experiments to determine the precise molecular role of WRN in mammalian cell recombination. Our experiments will lead to testing for genetic interactions with other repair/recombination components such as ERCC1 and MSH3. Our research goal is to examine the role of WRN in aging and cancer susceptibility, particularly in the context of environmental exposures to carcinogenic benzene metabolites.

Selected Publications

  1. Liu Y, Nairn RS, Vasquez KM. Processing of triplex-directed psoralen DNA interstrand crosslinks by recombination mechanisms, Nucleic Acids Res, 36 (14), 4680-8, 2008
  2. Rahn JJ, Trono D, Gimenez-Conti I, Butler AP, Nairn RS. Etiology of MNU-induced melanomas in Xiphophorus hybrids, Comp Biochem Physiol C Toxicol Pharmacol, 2008
  3. Talbert LL, Coletta LD, Lowery MG, Bolt A, Trono D, Adair GM, Nairn RS. Characterization of CHO XPF mutant UV41: Influence of XPF heterozygosity on double-strand break-induced intrachromosomal recombination, DNA Repair (Amst), 7 (8), 1319-29, 2008
  4. Butler AP, Trono D, Beard R, Fraijo R, Nairn RS. Melanoma susceptibility and cell cycle genes in Xiphophorus hybrids, Mol Carcinog, 46 (8), 685-91, 2007
  5. Mitchell D, Paniker L, Sanchez G, Trono D, Nairn R. The etiology of sunlight-induced melanoma in Xiphophorus hybrid fish, Mol Carcinog, 46 (8), 679-84, 2007
  6. Mitchell DL, Nairn RS. Photocarcinogenesis in Xiphophorus hybrid models, Zebrafish, 3 (3), 311-23, 2006
  7. Nairn RS, Adair GM. Use of gene targeting to study recombination in mammalian cell DNA repair mutants, Methods Mol Biol, 314, 133-54, 2006
  8. Richards S, Liu ST, Majumdar A, Liu JL, Nairn RS, Bernier M, Maher V, Seidman MM. Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways, Nucleic Acids Res, 33 (17), 5382-93, 2005

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9424