Dr. David G. Johnson
The University of Texas MD Anderson Cancer Center
Department of Molecular Carcinogenesis
The Virginia Harris Cockrell Cancer Research Center
My laboratory is located in Smithville, Texas, at UT Science Park
- Cancer genetics
- DNA damage response
- Cell cycle
My current research is focused on two transcription factors that respond to DNA damage and play important roles in regulating tumor development. The first project focuses on E2F1, a regulator of genes important for cell cycle progression and apoptosis. We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. Moreover, our studies demonstrate that E2F1 recruits chromatin-modifying enzymes to sites of damage to facilitate access to the DNA repair machinery. These findings indicate that E2F1 stimulates DNA repair through a non-transcriptional mechanism that functions in the context of chromatin. The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR.
The other project involves the study of a single nucleotide polymorphism (SNP) in the human p53 gene that results in either arginine (R) or proline (P) at position 72 of the p53 protein. This SNP affects the apoptotic activity of p53 but the mechanistic basis and physiologic relevance of this phenotypic difference remain unclear. We have developed mouse models that mimic this human SNP and have demonstrated that the humanized p53 variants are functional and display the expected difference in apoptotic capacity in mouse tissues. These models are being used to explore the roles of this human SNP in modulating cancer susceptibility and the response to DNA damaging agents, including chemotherapeutic drugs.
Chen J, Zhu F, Weaks RL, Biswas AK, Guo R, Li Y, Johnson DG. E2F1 Promotes the Recruitment of DNA Repair Factors to Sites of DNA Double-Strand Breaks. Cell Cycle 10(8). e-Pub 4/2011. PMID: 21448005.
Guo R, Chen J, Mitchell DL, Johnson DG. GCN5 and E2F1 stimulate nucleotide excision repair by promoting H3K9 acetylation at sites of damage. Nucleic Acids Res 39(4):1390-7, 3/2011. e-Pub 10/23/2010. PMCID: PMC3045616.
Zhu F, Dolle ME, Berton TR, Kuiper RV, Capps C, Espejo A, Mcarthur MJ, Bedford MT, van Steeg H, de Vries A, Johnson DG. Mouse Models for the p53 R72P Polymorphism Mimic Human Phenotypes. Cancer Res 70(14):5851-5859, 7/2010. e-Pub 6/2010. PMCID: PMC29095499.
Guo R, Chen J, Zhu F, Biswas AK, Berton TR, Mitchell DL, Johnson DG. E2F1 localizes to sites of UV-induced DNA damage to enhance nucleotide excision repair. J Biol Chem 285(25):19308-19315, 6/2010. e-Pub 4/2010. PMCID:PMC2885209.
Paulson QX, Pusapati RV, Hong S, Weaks RL, Conti CJ, Johnson D. Transgenic expression of E2F3a causes DNA damage leading to ATM–dependent apoptosis. Oncogene 27(36):4954-61, 8/2008. PMID: 18469863.
Pusapati RV, Rounbehler RJ, Hong SK, Powers JT, Yan M, Kiguchi K, McArthur M, Wong PK, Johnson DG. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Natl Acad Sci USA, 103(5):1446-1451, 1/2006. PMCID: PMC1345703.
Program in Molecular Carcinogenesis
Office: MDA SPRD SRD1.136 (Unit 116)
Ph.D. - The University of Texas-Southwestern Medical Center - 1991