Positions

Overview

  • Cellular DNA is continually altered by mutagenic agents from the environment (e.g. UV light, radiation etc.) and cellular metabolism (e.g. reactive oxygen). This DNA damage, and the resulting mutation, contributes to many interesting phenomena in biology– evolution, antibiotic resistance in bacteria, toxicity, initiation of cancerous cells in animals, treatments for cancer, to name a few. My lab is focused on the mechanisms that protect genes and genomes from excess DNA damage and mutation, using the plant Arabidopsis thaliana as a model system. Because the types of damage to DNA are so diverse, it is not surprising that the mechanisms and molecular pathways that monitor and repair DNA damage are very complex. What may be surprising, however, is that DNA maintenance and repair pathways are very well conserved, from single-celled microorganisms (such as yeasts), to plants, to humans. In other words, yeast and plant genomes encode the same general DNA repair pathways that are present in humans. Therefore, organisms such as yeasts and plants are useful “model systems” for the study of DNA repair and genome maintenance.

    Two general mechanisms that we are actively pursuing in the lab are the regulation of DNA repair pathways, and how cells monitor and regulate cell-cycle progression in response to DNA damage. When a cell incurs DNA damage, the cell must first recognize the type of damage, and then mount an appropriate response. This response is not simply just a decision of the type of repair pathway to activate (Non-homologous end joining versus recombinational repair, for example), but also involves activating so-called cell-cycle “checkpoints” if DNA damage persists, and in the case of animals often involves a cellular life or death decision termed apoptosis. Consequently, we are interested in identifying novel genes and pathways involved in the initial response to DNA damage in Arabidopsis thaliana to gain insights into how plant cells protect themselves from genomic stress, potentially leading to insights into animal DNA repair and maintenance.

    The protein kinases ATR and ATM are known master regulators of both the DNA repair and cell-cycle checkpoint responses to DNA damage in mammalian cells. These master regulators are key components of cellular decisions in how to respond appropriately to cellular DNA damage. Currently, my lab is interested in upstream activators of ATR and ATM. One example is activation of ATR pathways through Replication Protein A (RPA) by DNA damage. We have recently characterized a unique plant gene family of RPA, and are interested in how the various functions of RPA are integrated into the DNA damage response.

    Overall, our goal is to better understand the highly complex pathways involved in DNA repair and genome maintenance in Arabidopsis, and apply this knowledge to better improve crop species, and potentially aid in the understanding of these pathways in humans as it relates to disease and cancer biology.

    If you are currently an undergraduate (preferably majoring in biological sciences) in good academic standing, and would like to gain some research experience, please visit the COLSA Research Opportunities Webpage, to see what current opportunities are available in the lab.
  • Publications

    Academic Article

    Year Title
    2016 Corrigendum: High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.Frontiers in Plant Science.  7:1753. 2016
    2016 Molecular Evolution and Functional Diversification of Replication Protein A1 in Plants.Frontiers in Plant Science.  7:33. 2016
    2015 Genetic Analysis of Replication Protein A Large Subunit Family in Arabidopsis Reveals its Role in the DNA Damage Response PathwayFASAB J.  29. 2015
    2014 Genetic analysis of the Replication Protein A large subunit family in Arabidopsis reveals unique and overlapping roles in DNA repair, meiosis and DNA replication.Nucleic Acids Research.  42:3104-3118. 2014
    2014 High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.Frontiers in Plant Science.  5:364. 2014
    2009 The Arabidopsis ATRIP ortholog is required for a programmed response to replication inhibitors.Plant Journal.  60:518-526. 2009
    2009 Ribonucleotide reductase regulation in response to genotoxic stress in Arabidopsis.Plant Physiology.  151:461-471. 2009
    2008 Both ATM and ATR promote the efficient and accurate processing of programmed meiotic double-strand breaks.Plant Journal.  55:629-638. 2008
    2006 ATR and ATM play both distinct and additive roles in response to ionizing radiation.Plant Journal.  48:947-961. 2006
    2005 Ionizing radiation-dependent gamma-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related.Molecular Biology of the Cell Cell Regulation.  16:2566-2576. 2005
    2005 Maintenance of the plant genome under natural lightBMC Plant Biology.  5:S7-S7. 2005
    2004 ATR regulates a G2-phase cell-cycle checkpoint in Arabidopsis thaliana.Plant Cell.  16:1091-1104. 2004
    2003 Dissimilar mispair-recognition spectra of Arabidopsis DNA-mismatch-repair proteins MSH2*MSH6 (MutSalpha) and MSH2*MSH7 (MutSgamma).Nucleic Acids Research.  31:6027-6034. 2003
    2000 Arabidopsis MutS homologs-AtMSH2, AtMSH3, AtMSH6, and a novel AtMSH7-form three distinct protein heterodimers with different specificities for mismatched DNA.Plant Cell.  12:991-1002. 2000
    2000 Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins.Nucleic Acids Research.  28:463-471. 2000
    1997 DNA mismatch repair in plants. An Arabidopsis thaliana gene that predicts a protein belonging to the MSH2 subfamily of eukaryotic MutS homologs.Plant Physiology.  115:833-839. 1997
    1995 CUE1: A Mesophyll Cell-Specific Positive Regulator of Light-Controlled Gene Expression in Arabidopsis.Plant Cell.  7:1599-1610. 1995

    Conference Proceeding

    Year Title
    2013 A Comprehensive Genetic Analysis of the RPA70 Gene Family in Arabidopsis thaliana Reveals Unique and Overlapping Roles in DNA Repair, Replication, and MeiosisIn Vitro Cellular and Developmental Biology - Animal. S69-S69. 2013

    Teaching Activities

  • Doctoral Thesis Taught course 2019
  • Rsrch Exp/MCBS Taught course 2019
  • Doctoral Thesis Taught course 2018
  • Doctoral Research Taught course 2018
  • Doctoral Research Taught course 2017
  • Doctoral Research Taught course 2017
  • Adv Rsrch Exp/MCBS Taught course 2016
  • Doctoral Research Taught course 2016
  • Doctoral Research Taught course 2015
  • Doctoral Research Taught course 2015
  • Doctoral Research Taught course 2015
  • Rsrch Exp/MCBS Taught course 2015
  • Rsrch Exp/MCBS Taught course 2015
  • Adv Rsrch Exp/MCBS Taught course 2014
  • Doctoral Research Taught course 2014
  • Doctoral Research Taught course 2014
  • Rsrch Exp/MCBS Taught course 2014
  • Education And Training

  • B.S. Molecular Biology, University of California - San Diego
  • Ph.D. Cell and Molecular Biology, Oregon State University
  • Full Name

  • Kevin Culligan