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.

In a second project involving the investigation of mechanisms of sunlight carcinogenesis, we are using a biological model for melanoma in the aquarium fish Xiphophorus, which comprises platyfish and swordtail species. Genetic hybrids between certain platyfish and swordtail species exhibit a very high incidence of spontaneous melanoma formation, which follows simple genetic predictions. We are studying 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. In recent studies, we have cloned another member of this family, CDKN2D, from Xiphophorus and mapped it to the same Xiphophorus linkage group. It is interesting that these related genes both appear to be involved in susceptibility to melanoma formation in two very different organisms, demonstrating that melanoma susceptibility can have a strong genetic basis. We are currently performing experiments to determine how the CDKN2X gene, as well as other cell cycle genes, is regulated to understand its function in controlling cell growth in various Xiphophorus tumor models.

Selected Publications

  1. Butler AP, Trono D, Coletta LD, Beard R, Fraijo R, Kazianis S, Nairn RS. Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma, Comp Biochem Physiol C Toxicol Pharmacol, 145 (1), 145-55, 2007
  2. Mitchell DL, Nairn RS. Photocarcinogenesis in Xiphophorus hybrid models, Zebrafish, 3 (3), 311-21, 2006
  3. Nairn RS, Adair GM. Use of gene targeting to study recombination in mammalian cell DNA repair mutants, Methods Mol Biol, 314, 133-54, 2006
  4. 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
  5. Kazianis S, Nairn RS, Walter RB, Johnston DA, Kumar J, Trono D, Della Coletta L, Gimenez-Conti I, Rains JD, Williams EL, Mamerow MM, Kochan KJ, Scharti M, Vielkind JR, Volff JN, Woolcock B, Morizot DC. The genetic map of Xiphophorus fishes represented by 24 multipoint linkage groups, Zebrafish, 1 (3), 287-304, 2004
  6. Mitchell DL, Nairn RS, Johnston DA, Byrom M, Kazianis S, Walter RB. Decreased levels of (6-4) photoproduct excision repair in hybrid fish of the genus Xiphophorus, Photochem Photobiol, 79 (5), 447-52, 2004

Contact Information


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