Shen, Xuetong

Shen, Xuetong Ph.D.

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Research Interests

Chromatin responses to DNA damage, nuclear actin and related proteins

Current Research

We seek to answer basic questions concerning the regulation and maintenance of the eukaryotic genome, which is organized into chromatin. ATP-dependent chromatin remodeling carried out by large protein complexes (SWI/SNF family) is recognized as a major mode of chromatin modification. The research in my lab focuses on understanding how chromatin is remodeled to suit various nuclear functions, such as transcription and DNA repair, and how defects in chromatin remodeling might lead to cancer. We use the budding yeast as a model system, taking advantage of the powerful genetics, as well as the well-developed biochemical tools. Current research focuses on a novel and evolutionarily conserved class of ATP-dependent chromatin remodeling complexes, called the INO80 class. The study of the INO80 complex has led us to two main areas of research in the lab.

  1. Chromatin Responses to DNA damage
    Environmental exposures to DNA-damaging agents and genetic changes within the cell can lead to a variety of DNA damage, which causes genome instability and can eventually result in human diseases such as cancer. However, in vivo, eukaryotic DNA is packaged into chromatin; therefore, the damaged DNA exists in the context of chromatin, and the DNA repair machinery must deal with the chromatin environment. Eukaryotic cells utilize chromatin modifying complexes to regulate chromatin by ATP-dependent perturbations of histone-DNA interactions, or by covalent post-translational modification (PTM) of the histones. The long-term goal of our research is to understand how chromatin is modified to allow DNA repair to occur in an orderly fashion after DNA is damaged, and how changes in chromatin modification lead to human diseases, such as cancer. We and others have shown that the INO80 complex is a direct and key player in the repair of DNA double-strand breaks (DSBs), thus establishing a link between chromatin remodeling and DNA repair. Additional studies from our lab have shown that the INO80 complex is post-translationally modified upon DNA damage. Based on these studies, we propose that chromatin undergoes complex changes in response to DNA damage, which involve not only the histones, but also the chromatin modifying complexes. Studying how chromatin responds to DNA damage will contribute to our understanding of the mechanisms of genome instability and carcinogensis.
  2. Nuclear Actin and Related Proteins
    Recent advances in chromatin research have identified conventional actin, as well as actin-related proteins (Arps), as subunits of many chromatin modifying complexes. Like histones, actin is one of the most important and conserved molecules of the cell. While the roles of actin in the cytoplasm are well established, the presence and function of actin in the cell nucleus remain poorly defined. The mystery of nuclear actin has remained a challenge to biologists for several decades, due to the lack of a defined system in which the function of nuclear actin can be cleanly dissected biochemically and genetically. Taking advantages of the evolutionarily conserved actin- and Arp-containing INO80 chromatin remodeling complex and the yeast genetic system with a single actin gene, we have generated results showing that actin and Arps are stable and functional subunits of the INO80 complex. Our biochemical and genetic studies have established a defined system for the study of nuclear actin and Arps. Understanding the function and mechanism of the conserved actin and Arps in the nucleus has important implications in our basic understanding about chromatin and the cell nucleus.

Selected Publications

  1. Morrison AJ, Kim JA, Person MD, Highland J, Xiao J, Wehr TS, Hensley S, Bao Y, Shen J, Collins SR, Weissman JS, Delrow J, Krogan NJ, Haber JE, Shen X. Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses, Cell, 130 (3), 499-511, 2007
  2. Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery, Nature, 439 (7075), 497-501, 2006
  3. Mizuguchi G, Shen X, Landry J, Wu WH, Sen S, Wu C. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex, Science, 303 (5656), 343-8, 2004
  4. Morrison AJ, Highland J, Krogan NJ, Arbel-Eden A, Greenblatt JF, Haber JE, Shen X. INO80 and gamma-H2AX Interaction Links ATP-Dependent Chromatin Remodeling to DNA Damage Repair, Cell, 119 (6), 767-75, 2004
  5. Shen X, Ranallo R, Choi E. Involvement of actin-related proteins in ATP-dependent chromatin remodeling, Mol Cell, 12 (1), 147-155, 2003

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9450