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PMID:22383942

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Citation

Dittrich, CM, Kratz, K, Sendoel, A, Gruenbaum, Y, Jiricny, J and Hengartner, MO (2012) LEM-3 - A LEM domain containing nuclease involved in the DNA damage response in C. elegans. PLoS ONE 7:e24555

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.

Links

PubMed PMC3285610 Online version:10.1371/journal.pone.0024555

Keywords

Alleles; Animals; Apoptosis; Bacterial Proteins/metabolism; Caenorhabditis elegans; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/physiology; Cell Cycle; 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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EEN6

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ANKL1

enables

GO:0004520: endodeoxyribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:ANKL1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0000737: DNA catabolic process, endonucleolytic

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0009792: embryo development ending in birth or egg hatching

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00000235

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0010165: response to X-ray

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00000235

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006963

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0010165: response to X-ray

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00252143

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0010225: response to UV-C

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL1

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:EMR1

involved_in

GO:0010165: response to X-ray

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00145526

P

Seeded From UniProt

complete

CAEEL:BAF1

involved_in

GO:0009792: embryo development ending in birth or egg hatching

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002276

P

Seeded From UniProt

complete

CAEEL:BAF1

involved_in

GO:0010165: response to X-ray

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002276

P

Seeded From UniProt

complete

CAEEL:BAF1

involved_in

GO:0010165: response to X-ray

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00249180

P

Seeded From UniProt

complete

CAEEL:Q21302

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002276

P

Seeded From UniProt

complete

CAEEL:Q21302

involved_in

GO:0010225: response to UV-C

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00091982

P

Seeded From UniProt

complete

CAEEL:LEM2

involved_in

GO:0010165: response to X-ray

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00250567

P

Seeded From UniProt

complete


See also

References

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