LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans
Copyright policy )LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans
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.
PLoS ONE, 7 (2)
ISSN:1932-6203
- ETH Zurich Switzerland
- Hebrew University of Jerusalem Israel
- University of Zurich Switzerland
- Swiss National Science Foundation Switzerland
Science, Apoptosis, Cell Cycle Proteins, 1100 General Agricultural and Biological Sciences, Bacterial Proteins, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Alleles, 1000 Multidisciplinary, Endodeoxyribonucleases, Models, Genetic, 10061 Institute of Molecular Cancer Research, Q, Cell Cycle, Genetic Complementation Test, R, Membrane Proteins, Nuclear Proteins, 10124 Institute of Molecular Life Sciences, Chromatin, Luminescent Proteins, Cross-Linking Reagents, Ethyl Methanesulfonate, Mutation, 570 Life sciences; biology, Medicine, Cisplatin, Research Article, DNA Damage
Science, Apoptosis, Cell Cycle Proteins, 1100 General Agricultural and Biological Sciences, Bacterial Proteins, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Alleles, 1000 Multidisciplinary, Endodeoxyribonucleases, Models, Genetic, 10061 Institute of Molecular Cancer Research, Q, Cell Cycle, Genetic Complementation Test, R, Membrane Proteins, Nuclear Proteins, 10124 Institute of Molecular Life Sciences, Chromatin, Luminescent Proteins, Cross-Linking Reagents, Ethyl Methanesulfonate, Mutation, 570 Life sciences; biology, Medicine, Cisplatin, Research Article, DNA Damage
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