Douglas Bishop, Ph.D.

Professor of Radiation and Cellular Oncology

Research Summary

Dr. Bishop focuses on the mechanisms cell use to repair broken DNA molecules. DNA breaks occur during normal cell growth, during meiosis, the special cell divisions that gives rise to gametes, and when cells are exposed to radiation. DNA repair is relevant to cancer in two ways. First, when normal cells fail to repair DNA, mutations occur and these mutations can lead to cancer. Second, many effective cancer treatments, such as radiation treatment, and some forms of chemotherapy, work because they kill tumor cells by damaging tumor cell DNA. In this case, DNA repair contributes to treatment failure by protecting tumor cells from the effects of therapeutic agents. Dr. Bishop uses genetic techniques to study the proteins that carry out a form of DNA repair called "recombinational repair" in yeast and vertebrate cells. The lab has recently identified a group of proteins that work as "assembly factors" to build the protein complexes needed to repair DNA. One of the proteins that appears to play the role of assembly factor is BRCA1p which is encoded by the BRCA1 gene. The BRCA1 gene helps prevent cancer, people who inherit defective copies of this gene have a high risk of breast cancer and other malignancies. In addition to studying recombination genes and proteins in more detail, Dr. Bishop is working in collaboration with Dr. Weischelbaum's group to identify inhibitors of recombination complex assembly. Their experiments have already provided evidence that assembly inhibitors will increase the effectiveness of certain types of chemotherapy.

In addition to studying the repair process itself, Dr. Bishop studies proteins that help cells recover from DNA damage by stopping cell growth when damage is present. The arrest caused by these proteins allows time for the DNA repair process to occur. Recent work from the Bishop lab indicates that the same proteins that halt cell growth after DNA damage also appear to be important for generating or maintaining normal chromosome structure.

Publications

  • Budke B, Logan HL, Kalin JH, Zelivianskaia AS, Cameron McGuire W, Miller LL, Stark JM, Kozikowski AP, Bishop DK, Connell PP. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012 May 9. [Epub ahead of print] PubMed PMID: 22573178.
  • Shah PP, Zheng X, Epshtein A, Carey JN, Bishop DK, Klein HL. Swi2/Snf2-related translocases prevent accumulation of toxid Rad51 complexes during mitotic growth. Mol Cell. 2010 Sep 24; 39(6):862-72. PubMed PMID: 20864034.
  • Ferrari SR, Grubb J, Bishop DK. The Mei5-Sae3 protein complex mediates Dmc1 acticity in Saccharomyces cerevisiae. J Biol Chem. 2009 May 1;284(18):11766-70. Epub 2009 Mar 7. PubMed PMID: 19270307. 
  • Jayathilaka K, Sheridan SD, Bold TD, Bochenska K, Logan HL, Weichselbaum RR, Bishop DK, Connell PP. A chemical compound that stimulated the human homologous recombination protein RAD 51. Proc Natl Acad Sci U S A. 2008 Oct 14; 105(41):15848-53. Epub 2008 Oct 7. PubMed PMID: 18840682.
  • Sheridan SD, Yu X, Roth R, Heuser JE, Sehorn MG, Sung P, Egelman EH, Bishop DK. A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments. Nucleic Acids Res. 2008 Jull 36(12):4057-66. Epub 2008 Jun 4. PubMed PMID: 18535008.