RRC ID 46058
Author Dittrich CM, Kratz K, Sendoel A, Gruenbaum Y, Jiricny J, Hengartner MO.
Title LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans.
Journal PLoS One
Abstract 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.
Volume 7(2)
Pages e24555
Published 2012-1-1
DOI 10.1371/journal.pone.0024555
PII PONE-D-11-14963
PMID 22383942
PMC PMC3285610
MeSH 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
IF 2.74
Times Cited 29
C.elegans tm3468 tm1582