Veronica M. Maher

Research Interests

In the past, Dr. Maher's research group has studied how defects in ability of human cells to repair DNA damage induced by various chemical carcinogens, ultraviolet radiation, or ionizing radiation leads to permanent changes (mutations) in the primary DNA sequence of genes, including cancer-related genes (oncogenes and suppressor genes). Her group developed methods for detecting DNA damage and rates of repair at the level of the nucleotide. Presently, she and her group of researchers are investigating the mechanisms involved in carcinogen-induced mutation induction by DNA damage that blocks replication and the mechanisms by which human cells are able to continue to replicate DNA that contains such lesions. They are investigating the roles played by a series of newly-discovered DNA polymerases, such as Pol Zeta (hRev3 and hRev7), hRev1, Pol Eta, Pol Iota, and Pol Kappa etc. Such polymerases in combination with one another, are capable of replicating past fork-blocking lesions in DNA, but at the cost of making errors (mutations). Therefore, they play a causal role in the development of cancer. Dr. Maher's research group has shown that, in addition to using these error-prone polymerases to continue replicating DNA containing fork-blocking lesions, human cells can make use of an undamaged homologous copy of the blocked gene to circumvent the replication problem. The latter mechanism, designated gene conversion or homologous recombination, is essentially error-free.

Recent Publications

Lito P, Mets BD, Kleff S, O'Reilly S, Maher VM, McCormick JJ. Evidence That Sprouty 2 Is Necessary for Sarcoma Formation by H-Ras Oncogene-transformed Human Fibroblasts. J Biol Chem. 2008 Jan 25;283(4):2002-9.

Wang Y, Woodgate R, McManus TP, Mead S, McCormick JJ, Maher VM. Evidence that in xeroderma pigmentosum variant cells, which lack DNA polymerase eta, DNA polymerase iota causes the very high frequency and unique spectrum of UV-induced mutations. Cancer Res. 2007 Apr 1;67(7):3018-26.

Lou Z, Maher VM, McCormick JJ. Identification of the promoter of human transcription factor Sp3 and evidence of the role of factors Sp1 and Sp3 in the expression of Sp3 protein. Gene. 2005 May 23;351:51-9. Epub 2005 Apr 25.

M. L. Fishel, M. P. Gamesik, E. G. Zuhowski, S.M. Delaney, V. M. Maher, T. Karrison, R. C. Moschel, M. J. Egorin, and M. E. Dolan. 2005. Role of glutathione and nucleotide excision repair in modulation of cisplatin activity with O6-benzylguanine. Cancer Chemotherapy and Pharmacology. 55, 333-342.

Z. Li, H. Zhang, T. P. McManus, J. J. McCormick, C. W. Lawrence, V. M. Maher. 2002. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol-epoxide-induced DNA lesions in human fibroblasts. Mut. Res. 510, 71-80.

Z. Li, W. Xiao, J. J. McCormick and V. M. Maher. 2002. Identification of a protein essential for a major pathway used by human cells to avoid UV-induced DNA damage Proc. Natl. Acad. Sci., USA, 99 4459-4464.

C. W. Lawrence and V. M. Maher. 2001. Eukaryotic mutagenesis and translesion replication dependent on DNA polymerase æ and Rev1 protein. Biochemical Society Transactions, New Frontiers in DNA Repair 29, part 2, 187-191.

C.W. Lawrence and V. M. Maher. 2001. Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p. Phil. Trans. Royal Society Lond. B 356, 41-46.

C.W. Lawrence, P.E.M. Gibbs, R.S. Murante, X-D. Wang, Z. Li, T.P. McManus, W.G. McGregor, J.R. Nelson, D.C. Hinkle, and V. M. Maher. 2000. Roles of DNA polymerase . and Rev1 protein in eukaryotic mutagenesis and translesion replication. Cold Spring Harbor Symposia on Quantitative Biology, Biological Responses to DNA Damage, Cold Spring Harbor Laboratory Press, vol. LXV, 61-69.

H. Zhang, G. Marra, B. Tung, J. Jiricny, V.M. Maher and J. J. McCormick. 2000. Postreplicative mismatch repair is required for O6-methylguanine-induced intrachromosomal homologous recombination in human fibroblasts. Carcinogenesis 20, 1639-1646.

S.E. Boley, T.P. McManus, V.M. Maher, and J.J. McCormick. 2000. Malignant transformation of human fibroblast cell strain MSU-1.1 by N-methyl-N-nitrosourea: evidence of elimination of p53 by homologous recombination. Cancer Res. 60, 4105-4111.

P.E. Gibbs, X.-D. Wang, Z. Li, T.P. McManus, W.G. McGregor, C.W. Lawrence, and V.M. Maher. 2000. The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by ultraviolet light. Proc. Natl. Acad. Sci. USA 97,4186-91. MORE