Reference - Detail
|Author||Lawrence KS, Tapley EC, Cruz VE, Li Q, Aung K, Hart KC, Schwartz TU, Starr DA, Engebrecht J.|
|Title||LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.|
|Journal||J Cell Biol|
The Caenorhabditis elegans SUN domain protein, UNC-84, functions in nuclear migration and anchorage in the soma. We discovered a novel role for UNC-84 in DNA damage repair and meiotic recombination. Loss of UNC-84 leads to defects in the loading and disassembly of the recombinase RAD-51. Similar to mutations in Fanconi anemia (FA) genes, unc-84 mutants and human cells depleted of Sun-1 are sensitive to DNA cross-linking agents, and sensitivity is rescued by the inactivation of nonhomologous end joining (NHEJ). UNC-84 also recruits FA nuclease FAN-1 to the nucleoplasm, suggesting that UNC-84 both alters the extent of repair by NHEJ and promotes the processing of cross-links by FAN-1. UNC-84 interacts with the KASH protein ZYG-12 for DNA damage repair. Furthermore, the microtubule network and interaction with the nucleoskeleton are important for repair, suggesting that a functional linker of nucleoskeleton and cytoskeleton (LINC) complex is required. We propose that LINC complexes serve a conserved role in DNA repair through both the inhibition of NHEJ and the promotion of homologous recombination at sites of chromosomal breaks.
|MeSH||Caenorhabditis elegans Proteins / metabolism* Cell Cycle Checkpoints / drug effects Cell Cycle Checkpoints / radiation effects Cell Nucleus / drug effects Cell Nucleus / metabolism Cell Nucleus / radiation effects Cell Proliferation / drug effects Cell Proliferation / radiation effects Cisplatin / pharmacology Cross-Linking Reagents / metabolism DNA Damage DNA End-Joining Repair* / drug effects DNA End-Joining Repair* / radiation effects Germ Cells / cytology Germ Cells / drug effects Germ Cells / metabolism Germ Cells / radiation effects Homologous Recombination* / drug effects Homologous Recombination* / radiation effects Humans Hydroxyurea / pharmacology Meiosis / drug effects Meiosis / radiation effects Membrane Proteins / metabolism Microtubule-Associated Proteins / metabolism Microtubules / drug effects Microtubules / metabolism Microtubules / radiation effects Models, Biological Multiprotein Complexes / metabolism* Nuclear Proteins / metabolism Polymerization / drug effects Protein Binding / drug effects Protein Binding / radiation effects Protein Transport / drug effects Protein Transport / radiation effects Radiation, Ionizing|
|C.elegans||tm1524 tm1145 tm1268 tm423|