Dr. Randy J. Legerski

Regular Member

The University of Texas MD Anderson Cancer Center
Department of Genetics

Primary Research Area: Molecular/Cellular Genetics; Secondary Research Area: Cancer Genetics

Research Interests:

• Eukaryotic DNA repair
• Cell cycle checkpoints
• Carcinogenesis

The overall objective of my laboratory is the study of molecular mechanisms of cellular responses to DNA damage in mammalian systems usually referred to as the DNA damage response or DDR. We are particularly interested in the relationship between these pathways and the degenerative processes of carcinogenesis and aging in humans. A current major focus is the mechanisms by which the cell cycle is regulated in response to DNA damage and other forms of cellular stress. Particularly we are interested in both the imposition of cell cycle arrest and the ultimate recovery from the checkpoint. In this regard, we are investigating the functions of a small gene family referred to as SNM1 ( sensitivity to nitrogen mustard). This family includes Artemis, Apollo, and SNM1A all of which we have demonstrated to have roles in cell cycle regulation in response to cellular stress. Our primary goal is the define the biochemical function of the proteins expressed by these three related genes.

A second goal of the laboratory is to define the mechanisms by which DNA interstrand cross-links (ICLs) are repaired in mammalian cells. Repair of ICLs is a significant topic for human health since important chemotherapeutic agents used against cancer and other diseases can induce these lesions. Repair of ICLs is poorly understood in mammalian cells and the elucidation of these pathways can lead to the development of more efficacious drugs, and the possible identification of targets for chemo-sensitization.


Selected Publications:

Wu Q, Christensen LA, Legerski RJ, Vasquez KM (2005) Mismatch Repair Participates in Processing Psoralen Interstrand Crosslinks in Human Cells. EMBO Reports 6, 551-560.

Ahkter S, Richie CT, Zhang N, Behringer RR, Zhu C, Legerski RJ (2005) Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection. Molec Cell Biol. 25, 10071-10078.

Zhang N, Kaur R, Lu X, Shen X, Li L, Legerski RJ (2005) The Pso4 mRNA Splicing and DNA Repair Complex Interacts with WRN for Processing of DNA Interstrand Cross-Links. J Biol Chem. 280, 40559-40567.

Geng L, Zhang X, Zheng S, Legerski RJ (2007) Artemis Links ATM to G2/M Checkpoint Recovery Via Regulation of Cdk1-Cyclin B. Molec. Cell. Biol. 27, 2625-2635.  

Zhang N, Liu X, Li L, Legerski RJ (2007) Double-Strand Breaks Induce Homologous Recombinational Repair of Interstrand Cross-Links via Cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi Anemia Pathway. DNA Repair 6, 1670-1678.

Additional Publications

Program Affiliations:

Program in Genes and Development

Program in Human and Molecular Genetics