Targeting homologous recombination in Notch-driven C. elegans stem cell and human tumors Academic Article uri icon

Overview

MeSH Major

  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Homologous Recombination
  • Neoplasms, Germ Cell and Embryonal
  • Receptors, Notch
  • Stem Cells

abstract

  • Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

publication date

  • June 29, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4485896

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0127862

PubMed ID

  • 26120834

Additional Document Info

start page

  • e0127862

volume

  • 10

number

  • 6