LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans

PLoS One. 2012;7(2):e24555. doi: 10.1371/journal.pone.0024555. Epub 2012 Feb 23.


The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage - possibly by promoting the reorganization of damaged chromatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Apoptosis
  • Bacterial Proteins / metabolism
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle
  • Cell Cycle Proteins
  • Chromatin / chemistry
  • Cisplatin / pharmacology
  • Cross-Linking Reagents / pharmacology
  • DNA Damage*
  • Endodeoxyribonucleases / chemistry
  • Endodeoxyribonucleases / physiology*
  • Ethyl Methanesulfonate / pharmacology
  • Genetic Complementation Test
  • Luminescent Proteins / metabolism
  • Membrane Proteins / chemistry
  • Models, Genetic
  • Mutation
  • Nuclear Proteins / chemistry
  • Phenotype
  • Protein Structure, Tertiary
  • Radiation, Ionizing
  • Subcellular Fractions
  • Transgenes
  • Ultraviolet Rays


  • Bacterial Proteins
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Cross-Linking Reagents
  • EMR-1 protein, C elegans
  • Luminescent Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • lem-2 protein, C elegans
  • yellow fluorescent protein, Bacteria
  • Ethyl Methanesulfonate
  • Endodeoxyribonucleases
  • LEM-3 protein, C elegans
  • Cisplatin