Adair, Gerald M.

Adair, Gerald M. Ph.D.

Selected Publications  |  Search PubMed  |  Contact

Research Interests

DNA repair and mutagenesis, homologous recombination, gene targeting

Current Research

A complex network of DNA repair and recombination processes work together to remove potentially mutagenic or carcinogenic damage from cellular DNA, in order to preserve genetic integrity and maintain genomic stability. Our studies are directed toward understanding the molecular/genetic mechanisms of DNA repair and recombination in mammalian cells, and the consequences of specific DNA repair or recombination deficiencies on mutation and genomic instability. We are using gene knockout/replacement approaches and DNA repair or recombination-deficient CHO cell lines to investigate functional interactions between key components of the nucleotide excision repair or DNA mismatch repair pathways, and homologous recombination pathways that play a major role in the repair of DNA double-strand breaks and interstrand crosslinks.

In collaboration with Dr. Rodney Nairn (this department), we have been investigating the roles of the ERCC1 and XPF nucleotide excision repair genes, the MSH3 mismatch repair gene, and the RAD52 and RAD51D double-strand break repair genes in homologous recombination and DNA interstrand crosslink repair. We are using targeted/intrachromosomal recombination assays to examine the frequencies and recombinant class distributions of homologous recombination events in mammalian cell lines that are deficient for either single or pair-wise combinations of key DNA repair or recombination genes. We have previously shown that both the ERCC1 and XPF gene products, which function together as the heterodimeric Xpf/Ercc1 endonuclease, are required for the removal of long non-homologous tails from the 3' ends of strand-invasion or single-strand-annealing recombination intermediates during homologous recombination. The Xpf/Ercc1 endonuclease has also been shown to be essential for repair of DNA interstrand crosslinks in mammalian cells. We are currently using isogenic wild-type, ERCC1 knockout, MSH3 gene-deleted, and compound-mutant MSH3 deleted/ERCC1 knockout cell lines to: (1) investigate the roles of the MSH3 mismatch repair gene and the MutSβ (Msh2/Msh3 heterodimer) mismatch repair complex in homologous recombination and repair of DNA interstrand crosslinks, and (2) determine whether MutSβ and Xpf/Ercc1 function together in the same or different recombination or crosslink repair pathways. Results obtained in our targeted recombination experiments using these isogenic cell lines have shown that MSH3 deleted cells are not seriously impaired in their ability to remove long end-blocking non-homologous tails from strand-invasion recombination intermediates. Compound mutant MSH3 deleted/ERCC1 knockout cells are unable to remove such tails, and display a quantitatively different and more severe recombination-deficient phenotype than either MSH3 deleted cells or an ERCC1 knockout cell line, indicating that Msh3 and Ercc1 are not epistatic for this recombination pathway.

Selected Publications

  1. Nairn RS, Adair GM. Use of gene targeting to study recombination in mammalian cell DNA repair mutants, Methods Mol Biol, 314, 133-54, 2006
  2. Adair GM, Rolig RL, Moore-Faver D, Zabelshansky M, Wilson JH, Nairn RS. Role of ERCC1 in removal of long non-homologous tails during targeted homologous recombination, Embo J, 19 (20), 5552-61, 2000
  3. Sargent RG, Meservy JL, Perkins BD, Kilburn AE, Intody Z, Adair GM, Nairn RS, Wilson JH. Role of the nucleotide excision repair gene ERCC1 in formation of recombination-dependent rearrangements in mammalian cells, Nucleic Acids Res, 28 (19), 3771-8, 2000

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9470