title: LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans.
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.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dittrich
authors.forename: Katja
authors.initials: K
authors.lastname: Kratz
authors.forename: Ataman
authors.initials: A
authors.lastname: Sendoel
authors.forename: Yosef
authors.initials: Y
authors.lastname: Gruenbaum
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000737:chemistry; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000502:physiology*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005816:Genetic Complementation Test; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011839:Radiation, Ionizing; D013347:Subcellular Fractions; D019076:Transgenes; D014466:Ultraviolet Rays
chemical_list: D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D003432:Cross-Linking Reagents; C573699:EMR-1 protein, C elegans; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C485768:lem-2 protein, C elegans; C054562:yellow fluorescent protein, Bacteria; D005020:Ethyl Methanesulfonate; D004706:Endodeoxyribonucleases; C574533:LEM-3 protein, C elegans; D002945:Cisplatin