Faculty

Tanya Paull

Paull, Tanya
Professor in Molecular Genetics & Microbiology
Howard Hughes Medical Institute Investigator

E-mail

Website

Main Office: MBB 2.448
Phone: (512) 232-7802

Alternate Office: MBB 2.448
Phone: (512) 232-7803

Mailing Address:
The University of Texas at Austin
Institute for Cellular and Molecular Biology (ICMB)
2500 Speedway Stop A4800
Austin, TX 78712-1191


Research Lab Students:
    Graduate Student
  • Arora, Sucheta - Graduate Student
  • Fu, Qiong - Graduate Student
  • Mand, Michael - Graduate Student
  • Yang, Soo-Hyun - Graduate Student
  • Zhou, Yi - Graduate Student
    Post Doctoral
  • Lee, Ji-Hoon - Post Doctoral
  • Makharashvili, Nodar - Post Doctoral
  • Zheng, Suting - Post Doctoral
    Staff
  • Deshpande, Rajashree - Staff
  • Sled, Lisa - Staff
  • Zhang, Xiaoming (Julie) - Staff


  • Research Summary:

    Research in the lab is focused on the DNA damage response in eukaryotic cells, specifically the checkpoint activation and DNA repair responses that occur immediately after the introduction of chromosomal double-strand breaks. Several components of these DNA damage response systems have been implicated as tumor suppressors in mammalian organisms, thus establishing these factors as major targets in the progression from normal to unregulated cell growth.

    Current studies in the lab are primarily focused on the biochemical activities of a complex of proteins, Mrell/Rad50/Nbs1 (M/R/N), which are critical components in the repair of DNA double-strand breaks. We study the activities of recombinant M/R/N complexes in vitro to characterize its functions on different types of DNA substrates and recombination intermediates. In addition, in vivo assays in S. cerevisiae are utilized to identify functions of the complex and the effects of mutant complexes in cells. Our overall goal is to decipher the functions of each of these factors at a molecular level in order to understand how they cooperate to guard cells against genetic rearrangements and transformation.

    The M/R/N complex works in concert with the Ataxia-Telangiectasia-Mutated (ATM) protein kinase that phosphorylates many downstream targets responsible for checkpoint activation and DNA damage signaling in eukaryotes. We have previously shown that MRN recruits ATM to broken DNA ends and activates its kinase activity at these sites. We are currently investigating the mechanisms through which ATM is activated, how post-translational modifications affect this process, and how other ATM-interacting factors influence its regulation. We have also recently found that ATM can be activated in an MRN-independent manner through direct oxidation. This pathway is important for cellular control of antioxidant functions and for global responses of human cells to reactive oxygen species. The mechanism and targets of ATM activation through this pathway are currently being investigated.

    Research Images:



     
    Publications:
    2013Lee, J-H. Mand, M.R. Deshpande, R. Kinoshita, E. Yang, S. H. Wyman, C. Paull, T. T., Ataxia Telangiectasia-Mutated (ATM) Kinase Activity Is Regulated by ATP-driven Conformational Changes in the Mre11/Rad50/Nbs1 (MRN) Complex, J. Biol. Chem. 288:12840-51.
    2013Yang S-H, Zhou R, Campbell J, Chen J, Ha T, Paull TT , The SOSS1 single-stranded DNA binding complex promotes DNA end resection in concert with Exo1. , EMBO Journal 32:126-139.
    2010Nicolette ML, Lee K, Guo Z, Rani M, Chow JM, Lee SE, Paull TT., Mre11-Rad50-Xrs2 and Sae2 promote 5' strand resection of DNA double-strand breaks, Nat Struct Mol Biol. 17:1478-1485.
    2010Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT., ATM activation by oxidative stress, Science 330:517-521.
    2010Lee JH, Goodarzi AA, Jeggo PA, Paull TT., 53BP1 promotes ATM activity through direct interactions with the MRN complex, EMBO Journal 29:574-585.
    2008Hopkins BB, Paull TT., The P. furiosus mre11/rad50 complex promotes 5' strand resection at a DNA double-strand break., Cell 135:250-260.
    2007Lengsfeld, B.M., Rattray, A.J., Bhaskara, V., Ghirlando, R., and Paull, T.T. , Sae2 Is an Endonuclease that Processes Hairpin DNA Cooperatively with the Mre11/Rad50/Xrs2 Complex, Molecular Cell 28:638-651.
    2007Bhaskara, V., Dupre, A., Lengsfeld, B., Hopkins, B. B., Chan, A., Lee, J. H., Zhang, X., Gautier, J., Zakian, V. A., and Paull, T. T. , Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 complexes, Molecular Cell 25:647-661.
    2005Lee, J. H. and Paull, TT, ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex, Science 308:551-554.

     
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