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Randy J Legerski, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor, The University of Texas Graduate School of Biomedical Sciences, Houston, TX

Research Interests

  • Cellular responses to DNA damage
  • DNA repair
  • Cell cycle checkpoint signaling

The overall objective of my laboratory is the study of molecular mechanisms of cellular responses to DNA damage in mammalian systems. We are particularly interested in the relationship between these pathways and the degenerative processes of carcinogenesis and aging in humans. Our current focus is on the mechanisms of repair of interstrand cross-links in DNA. Repair of interstrand cross-links is a significant topic for human health since important chemotherapeutic agents used against cancer and other diseases can induce these lesions. In addition, food sources and mammalian metabolism can produce cross-linking agents that lead to DNA damage and genomic instability in cells. Genetic studies, primarily in yeast, have shown that homologous recombination is a primary pathway of cross-link repair; however, the early steps of damage recognition and processing of these lesions are still undefined. To investigate these pathways, we have developed a mammalian cell-free biochemical assay that has allowed us to begin identifying factors involved in this pathway and to elucidate the repair mechanisms. Using this in vitro assay, we have purified several factors involved in the initial stages of cross-link repair, and their characterization is currently a major focus of the laboratory. Our long-term goal is to completely reconstitute the mammalian interstrand cross-link repair pathway.

In addition to our biochemical studies, we are also focusing on the characterization of a small mammalian gene family whose homologue in yeast is specifically involved in cross-link repair. The snm1 (sensitivity to nitrogen mustard) mutant of Saccharomyces cerevisiae was first identified in a screen for strains sensitive to bifunctional alkylating agents. We have identified three mammalian homologues of this gene, SNM1, SNM1B and Artemis, and are currently characterizing their functions in mammalian cells. In constrast to the role scSNM1 we have found that SNM1 and Artemis are involved in mediating cell cycle checkpoints in mammalian cells in response to both DNA damage and mitotic stress. We are continuing to use biochemical, molecular biological and genetic approaches, including gene-targeting strategies in the mouse, to elucidate the function of the mammalian SNM1 genes.

 View a complete list of Dr. Legerski's publications.

Office Address

The University of Texas MD Anderson Cancer Center
Department of Genetics Unit 1010
1515 Holcombe Blvd.
Houston, TX 77030
Room Number: BSRB S13.8116B
Phone: (713) 834-6363

Education & Training

Degree-Granting Education

1977 University of Houston, Houston, TX, PHD, Biophysical Chemistry

Postgraduate Training

3/1979-4/1980 NIH Postdoctoral Fellowship, The University of Texas System Cancer Center, Houston, TX, Donald Robberson
4/1977-2/1979 NIH Postdoctoral Fellowship, Yale University, New Haven, CT, Joan Steitz

Selected Publications

Peer-Reviewed Original Research Articles

1. Zhang N, Kaur R, Akhter S, Legerski RJ. Cdc5L Interacts with ATR and Is Required for the S Phase Cell Cycle Checkpoint. EMBO Rep 10(9):1029-35, 9/2009. e-Pub 7/2009. PMCID: PMC2750050.
2. Wang H, Zhang X, Geng L, Teng L, Legerski RJ. Artemis Regulates Cell Cycle Recovery from the S Phase Checkpoint by Promoting Degradation of Cyclin E. J Biol Chem 284(27):18236-43, 7/2009. e-Pub 5/2009. PMCID: PMC2709338.
3. Zhang X, Zhu Y, Geng L, Wang H, Legerski RJ. Artemis is a Negative Regulator of p53 in Response to Oxidative Stress. Oncogene 28(22):2196-204, 6/2009. e-Pub 4/2009. PMCID: PMC2692457.
4. Geng L, Zhang X, Zheng S, Legerski RJ. Artemis links ATM to G2/M checkpoint recovery via regulation of Cdk1-cyclin B. Mol Cell Biol 27(7):2625-35, 4/2007. e-Pub 1/2007. PMCID: PMC1899901.
5. Akhter S, Richie CT, Deng JM, Brey E, Zhang X, Patrick C, Jr, Behringer RR, Legerski RJ. Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress. Mol Cell Biol 24(23):10448-55, 12/2004. PMCID: PMC529044.
6. Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ. Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. Mol Cell Biol 24(20):9207-20, 10/2004. PMCID: PMC517881.
7. Zhang N, Lu X, Zhang X, Peterson CA, Legerski RJ. hMutSβ is required for the recognition and uncoupling of psoralen interstrand cross-links in vitro. Mol Cell Biol 22(7):2388-97, 4/2002. PMCID: PMC133700.
8. Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell 82(4):555-64, 8/1995. PMID: 7664335.
9. Li L, Bales ES, Peterson CA, Legerski RJ. Characterization of molecular defects in xeroderma pigmentosum group C. Nat Genet 5(4):413-7, 12/1993. PMID: 8298653.
10. Legerski R, Peterson C. Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C. Nature 359(6390):70-3, 9/1992. PMID: 1522891.

Last updated: 1/26/2015